The human microbiome or microbiota represents diverse viral, bacterial, fungal, and other species that live on and within us. They are part of us and we are part of this complex ecosystem. The human body contains >10 times more microbial cells than human cells. Skin supports a range of microbial communities that live in distinct niches. Microbial colonization of skin is more dense in humid intertriginous and occluded sites such as axillae, anogenital regions, and webspaces of feet. An intact stratum corneum is the most important defense against invasion of pathogenic bacteria.
Coagulase-negative staphylococci normally colonize skin shortly after birth and are not considered to be pathogens when cultured from skin.
Overgrowth of flora in occluded areas of results in clinical syndromes of erythrasma, pitted keratolysis, and trichomycosis.
Pyoderma is an archaic term, literally “pus in the skin.” Skin and soft-tissue infections, commonly caused by Staphylococcus aureus and group A streptococcus (GAS), have been referred to a “pyoderma.” Pyoderma gangrenosum is a noninfectious inflammatory process, often associated with a systemic disorder such as inflammatory bowel disease.
S. aureus colonizes the nares and intertriginous skin intermittently, can penetrate the stratum corneum, and cause skin infections, e.g., impetigo, folliculitis. Deeper infection results in soft-tissue infections. Methicillin-resistant S. aureus (MRSA) is an important pathogen for community-acquired (CA-MRSA) and healthcare-acquired (HA-MRSA) infections. MRSA strain USA300 is the major cause of skin and soft tissue as well as more invasive infections in community and health-care settings.
GAS usually colonizes the skin first and then the nasopharynx. Group B streptococcus (GBS; Streptococcus agalactiae) and group G β-hemolytic streptococci (GGS) colonize the perineum of some individuals and may cause superficial and invasive infections.
Cutaneous production of toxins by bacteria (S. aureus and GAS) causes systemic intoxications such as toxic shock syndrome (TSS) and scarlet fever.
Erythrasma ICD-9: 039.0 ICD-10: L08.1
Etiology.Corynebacterium minutissimum, grampositive (diphtheroid) bacillus; normally in human microbiome. Growth favored by humid cutaneous microclimate.
Asymptomatic except for subtle discoloration.
Patches, sharply marginated (Fig. 25-1). Tan or pinkish; postinflammatory hyperpigmentation in more heavily pigmented individuals.
Figure 25-1. Erythrasma: axillaSharply marginated, red patch in the axilla. Wood’s lamp demonstrates bright coral-red, differentiating erythrasma from intertriginous psoriasis. KOH preparation was negative for hyphae.
In webspaces of feet, may be macerated (Fig. 25-2). Distribution: intertriginous skin, i.e., toe webs (Fig. 25-2), inguinal folds, axillae, other occluded sites.
Figure 25-2. Erythrasma: webspaceThis macerated interdigital webspace appeared bright coral-red when examined with Wood’s lamp; KOH preparation was negative for hyphae. The webspace is the most common site for erythrasma in temperate climates. In some cases, interdigital tinea pedis and/or pseudomonal intertrigo may coexist.
Wood’s lamp examination demonstrates corral-red fluorescence. KOH negative; rule out epidermal dermatophytosis.
Intertriginous psoriasis, epidermal dermatophytosis, pityriasis versicolor, Hailey-Hailey disease.
Persists and recurs unless microclimate is altered.
Usually controlled with benzoyl peroxide wash or sanitizing alcohol gel. Clindamycin lotion and erythromycin are beneficial.
Etiology.Kytococcus Sedentarius. One of human microbiome on plantar feet in the setting of hyperhidrosis; produces two extracellular proteases that can digest keratin.
Punched out pits in stratum corneum, 1-8 mm in diameter (Fig. 25-3). Pits can remain discrete or become confluent, forming large areas of eroded stratum corneum. Lesions are more apparent with hyperhidrosis and maceration. Symmetric or asymmetric involvement of both feet. Distribution: Pressure-bearing areas, ventral aspect of toe, ball of foot, heel; interface of toes.
Figure 25-3. Pitted keratolysis: plantarThe stratum corneum of the anterior plantar foot shows erosion with well-demarcated scalloped margins, formed by the confluence of multiple, confluent "pits" (defects in the stratum corneum).
Clinical diagnosis. KOH to rule out tinea pedis.
Concomitant tinea pedis, erythrasma, candidal intertrigo, and pseudomonal webspace infection may be present.
Persists and recurs unless microclimate is altered.
Usually controlled with benzoyl peroxide wash or sanitizing alcohol gel.
Trichomycosis ICD-9: 039.0 ICD-10: A48.8/L08.8
Superficial colonization on hair shafts in sweaty regions, axillary and pubic.
Etiology.Corynebacterium tenuis and other corynebacterial species; gram-positive diphtheroid. Not fungus.
Granular concretions (yellow, black, or red) on hair shaft (Fig. 25-4). Hair appears thickened, beaded, firmly adherent. Insoluble adhesive may erode cuticular and cortical keratin.
Treatment. Usually controlled with benzoyl peroxide wash or sanitizing alcohol gel. Antiperspirants. Shaving area.
Figure 25-4. Trichomycosis axillaris 40-year-old obese male. Axillary hairs have cream-color encrustation. Numerous skin tags are also seen.
Intertrigo ICD-9: 695.89 ICD-10: L30.4
Intertrigo (Latin inter, "between"; trigo, "rubbing").
Inflammation of opposed skin (inframammary regions, axillae, groins, gluteal folds, redundant skin folds of obese persons). May represent inflammatory dermatosis or superficial colonization or infection.
Dermatoses occurring in intertriginous skin. Intertriginous psoriasis. Also seborrheic dermatitis, Hailey–Hailey disease, Langerhans cell histiocytosis. S. aureus and streptococcus can cause secondary infection of these dermatoses.
• Beta-hemolytic streptococci. Group A (Fig. 25-5), group B, group G (Fig. 25-6). Streptococcal intertrigo can progress to soft-tissue infection (Fig. 25-6).
• S. aureus. Often gains entry into skin via hair follicle, causing folliculitis and furuncles.
• Pseudomonas aeruginosa (Fig. 25-7).
• C. minutissimum (erythrasma) (Figs. 25-1 and 25-2). K. sedentarius (pitted keratolysis) (Fig. 25-3).
Figure 25-5. Intergluteal intertrigo: group A streptococcus A painful moist erythematous plaque in a male with intertriginous psoriasis, with foul odor. Infection resolved with penicillin VK.
Figure 25-6. Erysipelas: group G streptococcus 65-year-old male with sharply marginated erythematous plaque on buttocks. Portal of entry of infection was intergluteal intertrigo.
Figure 25-7. Webspace intertrigo: P. aeruginosa Erosion of a webspace of the foot with a bright red base and surrounding erythema. Tinea pedis (interdigital and moccasin patterns) and hyperhidrosis were also present, which facilitated growth of Pseudomonas.
Usually asymptomatic. Discomfort usually indicates infection rather than colonization. Soft-tissue infection can gain entry in S. aureus or streptococcal intertrigo.
Identify pathogen by bacterial culture, Wood’s lamp examination, or KOH preparation.
Identify and treat pathogen.
Impetigo ICD-9: 686.80 ICD-10: B08.0
Etiology. S. aureus; GAS.
Portal of Entry. Impetigo occurs adjacent to the site of S. aureus colonization such as the nares (see Fig. 25-9). Secondary infection of (1) minor breaks in the epidermis (impetiginization), (2) of preexisting dermatoses, (3) other infections such as eczema herpeticum, or (4) wounds.
Clinical Manifestation. Crusted erosions.
Topical antibiotic to infected and colonized sites; systemic antibiotic.
Epidemiology and Etiology
• S. aureus: methicillin-sensitive (MSSA) and methicillin-resistant (MRSA). Bullous impetigo: local production of epidermolytic toxin A-producing S. aureus, which also causes staphylococcal scalded skin syndrome.
• Beta-hemolytic streptococcus: group A.
S. aureus and GAS are not members of human skin microbiome. They may transiently colonize skin and cause superficial infections.
Demography. Secondary infections, any age. Primary infections most often occur in children.
Portals of Entry of Infection. Minor breaks in the skin most commonly. Facial lesions usually associated with S. aureus colonization of nares. Dermatoses such as atopic dermatitis or Hailey–Hailey disease. Traumatic wounds. Bacterial infections occur in other cutaneous infections.
Superficial infections often asymptomatic. Ecthyma may be painful and tender. Most superficial bacterial infections of the skin cannot be categorized as “impetigo.”
Impetigo. Erosions with crusts (Figs. 25-8 and 25-9). Golden-yellow crusts are often seen in impetigo but are hardly pathognomonic; 1- to >3-cm lesions; central healing often apparent if lesions present for several weeks (Fig. 25-9). Arrangement: scattered, discrete lesions; without therapy, lesions may become confluent; satellite lesions occur by autoinoculation. Secondary infection of various dermatoses is common (Figs. 25-10 and 25-11).
Figure 25-8. Impetigo: MSSA Crusted erythematous erasions becoming confluent on the nose, cheek, lips, and chin in a child with nasal carriage of S. aureus and mild facial eczema.
Figure 25-9. Impetigo: MRSA 45-year-old male with large crusted erosions, becoming confluent, with central clearing on the face. MRSA colonized the nares.
Figure 25-10. Secondary infection of Hailey-Hailey disease: MRSA 51-year-old female with Hailey-Hailey disease has chronic MRSA infection of cutaneous erosions on thigh.
Figure 25-11. Secondary infection of pemphigus foliaceus: MRSA 65-year-old female with recalcitrant pemphigus foliaceus has extensive infection of cutaneous erosions on the face.
Bullous Impetigo. Blisters containing clear yellow or slightly turbid fluid with erythematous halo, arising on normal-appearing skin (see “Localized Form” of “Staphylococcal-Scalded Skin Syndrome"). With rupture, bullous lesions decompress. If roof of bulla is removed, shallow moist erosion forms (Figs. 25-12 and 25-13). Distribution: more common in intertriginous sites.
Figure 25-12. Bullous impetigo Scattered, discrete, intact, and ruptured thin-walled blisters on the inguinal area and adjacent thigh of a child; lesions in the groin have ruptured, resulting in superficial erosions.
Figure 25-13. Bullous impetigo with blistering dactylitis: S. aureus A large, single bulla with surrounding erythema and edema on the thumb of a child; the bulla has ruptured and clear serum exudes.
Ecthyma. Ulceration with a thick adherent crust (Fig. 25-14). Lesions may be tender, indurated.
Figure 25-14. Ecthyma: MSSA Thickly crusted erosion/ulcer on the nose had been present for 6 weeks, arising at the site of a small wound. The crust was adherent and the site bled with debridement.
Impetigo. Excoriation, allergic contact dermatitis, herpes simplex, epidermal dermatophytosis, scabies. Most erosions with “honey-colored crusts” are not impetigo.
Intact Bullae. Acute allergic contact dermatitis, insect bites, thermal burns, porphyria cutanea tarda (PCT) (dorsa of hands).
Ecthyma. Excoriations, excoriated insect bites, PCT, venous (stasis) and ischemic ulcers (legs).
Clinical findings confirmed by culture: S. aureus, commonly; failure of oral antibiotic suggests MRSA. GAS.
Untreated, lesions of impetigo become more extensive and ecthyma. With adequate treatment, prompt resolution. Lesions can progress to deeper skin and soft-tissue infections. Nonsuppurative complications of GAS infection include guttate psoriasis, scarlet fever, and glomerulonephritis. Ecthyma may heal with scarring. Recurrent S. aureus or GAS infections can occur because of failure to eradicate pathogen or by recolonization. Undiagnosed MRSA infection does not respond to usual oral antibiotics given for methicillin-sensitive S. aureus.
Prevention. Benzoyl peroxide wash. Check family members for signs of impetigo. Ethanol or isopropyl gel for hands and/or involved sites.
Topical Treatment. Mupirocin and retapamulin ointment is highly effective in eliminating S. aureus from the nares and cutaneous lesions.
Systemic Antimicrobial Treatment. According to sensitivity of isolated organism.
Abscess, Furuncle, Carbuncle
ICD-9: 680.9/682.9 ICD-10: L02
Deeper skin infections can follow traumatic inoculation into skin or extension of infection into hair follicles.
Abscess: Acute or chronic localized inflammation, associated with a collection of pus accumulated in a tissue. Inflammatory response to an infectious process or foreign material.
Folliculitis: Infection of hair follicle with ± pus in the ostium of follicle (see Section 31).
Furuncle: Acute, deep-seated, red, hot, tender nodule or abscess (boil) that evolves from a staphylococcal folliculitis.
Carbuncle: Deeper infection composed of interconnecting abscesses usually arising in several contiguous hair follicles.
Epidemiology and Etiology
S. aureus (MSSA, MRSA).
Other Organisms. Much less common.
Sterile abscess can occur as a foreign-body response (splinter, ruptured inclusion cyst, injection sites). Cutaneous odontogenic sinus can appear anywhere on the lower face, even at sites distant from the origin (see Fig. 33-23).
Folliculitis, furuncles, and carbuncles represent a continuum of severity of S. aureus infection. Portal of entry: ostium of hair follicle.
Folliculitis may be slightly tender. With deeper infection, pain and tenderness. Carbuncles may be accompanied by low-grade fever and malaise; lesions are red, hot, and painful/tender.
Abscess. May arise in any organ or tissue. Abscesses that present on the skin arise in the dermis, subcutaneous fat, muscle, or a variety of deeper structures. Initially, a tender red nodule forms. In time (days to weeks), pus collects within a central space (Fig. 25-15). A well-formed abscess is characterized by fluctuance of the central portion of the lesion. Arise at sites of trauma. Ruptured inclusion cyst on the back often present as painful abscess. When arising from S. aureus folliculitis, may be solitary or multiple.
Figure 25-15. Abscess: MSSA A very tender abscess with surrounding erythema on the heel. The patient was a diabetic patient with sensory neuropathy; puncture by a sewing needle that was imbedded in the heel had provided a portal of entry. The foreign body was removed surgically.
Folliculitis (Staphylococcal). See “Infectious Folliculitis” in Section 31.
Furuncle. Initially, a firm tender nodule, up to 1-2 cm in diameter. In many individuals, furuncles occur in setting of staphylococcal folliculitis. Nodule becomes fluctuant, with abscess formation ± central pustule. Nodule with cavitation remains after drainage of abscess. A variable zone of cellulitis may surround the furuncle. Distribution: any hair-bearing region—beard area, posterior neck and occipital scalp, axillae, buttocks. Solitary or multiple lesions (Figs. 25-16 to 25-20).
Figure 25-16. Furuncle: MSSA Abscess on the medial thigh of a 52-year-old male. The lesion was incised and drained and treated with doxycycline.
Figure 25-17. Furuncles and cellulitis: MRSA A 64-year-old male developed furuncles on the dorsum of the left hand (A) and forearm (B). He had a fistula on his forearm and was dialyzed three times per week. Infection was spreading from the abscess with cellulitis.
Figure 25-18. Multiple furuncles on the abdomen: MRSA 66-year-old operating room technician with multiple painful nodules. MRSA was isolated on culture of the nares and an abscess. He was treated with doxycycline, mupirocin to nares, and bleach baths. He was restricted from returning to work until cultured sites were negative for S. aureus colonization.
Figure 25-19. Multiple furuncles: MRSA Multiple painful nodules on the buttocks of a 44-year-old male with HIV disease.
Figure 25-20. Chronic abscess, botryomycosis: MRSA 41-year old with HIV disease had an extensive abscess for months, (A) R-buttock abscess, (B) The abscess was drained and treated with linezolid. (C) The white grains noted in the drainage represent colonies of S. aureus.
Carbuncle. Evolution is similar to that of furuncle. Composed of several to multiple, adjacent, coalescing furuncles (Fig. 25-21). Characterized by multiple loculated dermal and subcutaneous abscesses, superficial pustules, necrotic plugs, and sieve-like openings draining pus.
Figure 25-21. Carbuncle: MSSA A very large, inflammatory plaque studded with pustules, draining pus, on the nape of the neck. Infection extends down to the fascia and has formed from a confluence of many furuncles.
Painful Dermal/Subcutaneous Nodule. Ruptured epidermoid or pilar cyst, hidradenitis suppurativa (axillae, groin, vulva).
Clinical findings confirmed by findings on Gram staining and culture.
Most abscesses resolve with effective treatment. If diagnosis and treatment are delayed, furunculosis can be complicated by soft-tissue infection, bacteremia, and hematogenous seeding of viscera. Some individuals are subject to recurrent furunculosis, particularly diabetics.
The treatment of an abscess, furuncle, or carbuncle is incision and drainage plus systemic antimicrobial therapy.
Characterized by inflammation of skin and adjacent subcutaneous tissues. Soft tissue refers to tissues that connect, support, or surround other structures and organs: skin, adipose tissue, fibrous tissues, fascia, tendon, ligaments.
Syndromes. Cellulitis, erysipelas, lymphangitis, necrotizing fasciitis, wound infection.
Soft-Tissue Inflammation. Although often infectious, soft-tissue inflammation can be a manifestation of a noninfectious reaction pattern such as with neutrophilic dermatoses, erythema nodosum, and eosinophilic cellulitis.
Cellulitis. Usually begins at a portal of entry in the skin, spreading proximally as an expanding solitary lesion. Uncommonly, soft-tissue infection can follow hematogenous dissemination with multiple sites of infection. Cellulitis is most often acute, caused by S. aureus.
Acute Inflammation. Due to cytokines and bacterial superantigens rather than to overwhelming tissue infection.
Chronic Soft-Tissue Infection. Nocardiosis, sporotrichosis, and phaeohyphomycosis.
Cellulitis ICD-9: 035 ICD-10: A46.0
Acute, spreading infection of dermal and subcutaneous tissues. Characterized by a red, hot, tender area of skin. Portal of entry of infection is usually apparent. Most common pathogen is S. aureus. Erysipelas is a variant of cellulitis involving cutaneous lymphatics, and is usually caused by beta-hemolytic streptococci.
Epidemiology and Etiology
Etiology.Adults: S. aureus, GAS.
Less commonly beta-homolytic streptococcus: group B, C, or G. Erysipelothrix rhusiopathiae (erysipeloid); P. aeruginosa, Pasteurella multocida, Vibrio vulnificus; Mycobacterium fortuitum complex. In children: pneumococci, Neisseria meningitidis group B (periorbital). Haemophilus influenzae type b (Hib) infections much less common because of Hib immunization.
Chronic Soft-Tissue Infections. Nocardia brasiliensis, Sporothrix schenckii, Madurella species, Scedosporium species, nontuberculous mycobacteria (NTM).
Dog and Cat Saliva and Bites: P. multocida and other Pasteurella species. Capnocytophaga canimorsus (see Fig. 25-55).
Portal of Infection. Pathogens gain entry via any break in the skin or mucosa. Tinea pedis and leg and foot ulcers are common portals. Infections follow bacteremia/sepsis with cutaneous seeding.
Risk Factors. Host defense defects, diabetes mellitus, drug and alcohol abuse, cancer and cancer chemotherapy, chronic lymphedema [postmastectomy (see Fig. 25-25), previous episode of cellulitis/erysipelas].
After entry, infection spreads to tissue spaces and cleavage planes (Fig. 25-22) as hyaluronidases break down polysaccharide ground substances, fibrinolysins digest fibrin barriers, lecithinases destroy cell membranes. Local tissue devitalization is usually required to allow for significant anaerobic bacterial infection. The number of infecting organisms is usually small, suggesting that cellulitis may be more of a reaction to cytokines and bacterial superantigens than to overwhelming tissue infection.
Figure 25-22. Structural components of the skin and soft tissue, superficial infections, and infections of the deeper structures. The rich capillary network beneath the dermal papillae plays a key role in the localization of infection and in the development of the acute inflammatory reaction. [From Stevens DL. Infections of the skin, muscles, and soft tissues. In Longo DL et al. (eds.). Harrison’s Principles of Internal Medicine, 18th ed. New York, McGraw-Hill, 2012.]
Symptoms of fever and chills can develop before cellulitis is clinically apparent. Higher fever (3B.5°C) and chills usually associated with GAS infection. Local pain and tenderness. Necrotizing infections associated with more local pain and systemic symptoms.
Red, hot, edematous, shiny plaque originating at the portal of entry. Enlarges with proximal extension (Figs. 25-23 and 25-24); borders usually sharply defined, irregular, and slightly elevated. Vesicles, bullae, erosions, abscesses, hemorrhage, and necrosis may form in plaque (Fig. 25-24). Lymphangitis. Lymph nodes can be enlarged and tender, regionally.
Figure 25-23. Cellulitis at portal of entry: MSSA 51-year-old male with interdigital tinea pedis noted pain on the dorsum of his foot. KOH preparation was positive for dermatophytic hyphae. Methicillin-sensitive S. aureus was isolated on culture of the webspace.
Figure 25-24. Cellulitis lower leg: MRSA 70-year-old obese male with chronic venous stasis and stasis ulcer had increasing erythema and blister formation of the lower leg associated with fever.
Distribution. Adults. Lower leg most common site (Fig. 25-24). Arm: In young male, consider IV drug use; in female, postmastectomy (Fig. 25-25). Trunk: operative wound site. Face: following rhinitis, conjunctivitis, pharyngitis; associated with colonization of nares by S. aureus and of pharynx by GAS.
Figure 25-25. Recurrent cellulitis of the arm with chronic lymphedema: MSSA Right breast cancer had been treated with mastectomy and lymph node excision 10 years previously. Lymphedema of the right arm followed. Hand dermatitis was secondarily infected with MSSA. Cellulitis occurred repeatedly in the setting of chronic lymphedema.
Variants of Cellulitis by Pathogen
S. aureus: Portal of entry is usually apparent; cellulitis is an extension of focal infection. Toxin syndromes: scalded-skin syndrome, TSS. Endocarditis may follow bacteremia.
Beta-hemolytic streptococci GAS (Streptococcus pyogenes) colonize skin and oropharynx. GBS and GGS colonize anogenital region (Fig. 25-26). Beta-hemolytic streptococcal soft-tissue infections spread rapidly along superficial cutaneous lymphatic vessels, presenting a tender red expanding plaques, i.e., erysipelas (Fig. 25-27). Following childbirth, known as puerperal sepsis; infection can extend into pelvis. GBS cellulitis occurs in neonates; high morbidity and mortality. GAS infection with necrotizing fasciitis and streptococcal TSS has high morbidity and mortality.
Figure 25-26. Erysipelas of buttocks: group B streptococcus 40-year-old female with history of Crohn disease with ileostomy, prior surgery for hidradenitis, and invasive vulvar carcinoma; treated with radiation. Portal of entry was intergluteal cleft. Presented with fever and local tenderness for 1 day.
Figure 25-27. Erysipelas of face: group A streptococcus Painful, well-defined, shiny, erythematous, edematous plaques involving the central face of an otherwise healthy male. On palpation, the skin is hot and tender.
E. rhusiopathiae: Erysipeloid occurs in individuals who handle game, poultry, fish. Painful, inflamed plaque with sharply defined irregular raised border occurring at the site of inoculation, i.e., finger or hand (Fig. 25-28), spreading to wrist and forearm. Color: purplish red acutely; brownish with resolution. Enlarges peripherally with central fading. Usually no systemic symptoms.
Figure 25-28. Erysipeloid of hand A well demarcated, violaceous, cellulitic plaque (without epidermal changes of scale or vesiculation) on the dorsa of the hand and fingers, occurred following cleaning fish; the site was somewhat painful, tender, and warm.
Ecthyma gangrenosum: Rare variant of necrotizing soft-tissue infection caused by P. aeruginosa. Clinically characterized by infarcted center with erythematous halo, expanding rapidly without effective treatment (Fig. 25-29). Distribution: most commonly in the axilla, groin, perineum. Prognosis depends on prompt restoration of host defense defects, usually on correction of neutropenia. When occurring as a local infection in the absence of bacteremia, prognosis is much more favorable.
Figure 25-29. Ecthyma gangrenosum of buttock: P. aeruginosa A 30-year-old male with HIV disease and neutropenia. (A) An extremely painful, infarcted area with surrounding erythema present for 5 days. This primary cutaneous infection was associated with bacteremia. (B) Two weeks later, the lesion had progressed to a large ulceration. The patient died 3 months later of P. aeruginosa pneumonitisassociated with chronic neutropenia.
H. influenzae: Occurs mainly in children <2 years. Cheek, periorbital area, head, and neck are most common sites. Clinically, swelling, characteristic violaceous erythema hue. Use of Hib vaccine has dramatically reduced incidence.
V. vulnificus, V. cholerae non-01 and non-0139. Underlying disorders: cirrhosis, diabetes, immunosuppression, hemochromatosis, thalassemia. Follows ingestion of raw/under-cooked seafood, gastroenteritis, bacteremia with seeding of skin; also exposure of skin to seawater. Characterized by bulla formation, necrotizing vasculitis (Fig. 25-30). Usually on the extremities; often bilateral.
Figure 25-30. Bilateral cellulitis of legs: V. vulnificus Bilateral hemorrhagic plaques and bullae on the legs, ankles, and feet of an older diabetic with cirrhosis. Unlike other types of cellulitis in which microorganisms enter the skin locally, which is caused by V. vulnificus, usually follows a primary enteritis with bacteremia and dissemination to the skin. Most cases initially diagnosed as bilateral cellulitis are inflammatory (eczema, stasis dermatitis, psoriasis) rather than infectious.
Aeromonas hydrophila: Water-associated trauma; preexisting wound. Immunocompromised host. Lower leg. Necrotizing soft-tissue infection.
C. canimorsus. Immunosuppression or asplenia; exposure to dog saliva or bite. Causes fulminant sepsis and disseminated intravascular coagulation (see Fig. 25-57).
P. multocida: Most common cause of infection following animal bite; soft-tissue infection.
Clostridium species. Associated with trauma; contamination by soil or feces; malignant intestinal tumor. Infection characterized by gas production (crepitation on palpation), marked systemic toxicity. Necrotizing infection.
Nontuberculous mycobacteria (see p. 579). History of recent surgery, injection, penetrating wound, systemic corticosteroid therapy. Low-grade cellulitis. Multiple sites of infection. Systemic findings lacking.
Cryptococcus neoformans: Patient always immunocompromised. Red, hot, tender, edematous plaque on extremity. Rarely multiple noncontiguous sites.
Mucormycosis: Usually occurring in individual with uncontrolled diabetes.
Nocardiosis: See Cutaneous Nocardia Infections.
Eumycetoma: SeeSection 26.
Chromoblastomycosis: SeeSection 26.
Erysipelas/Cellulitis. Deep vein thrombophlebitis, early contact dermatitis, urticaria, insect bite (hypersensitivity response), fixed drug eruption, erythema nodosum, acute gout, erythema migrans (EM).
Necrotizing STIs. Vasculitis, embolism with infarction of skin, peripheral vascular disease, calciphylaxis, warfarin necrosis, traumatic injury, cryoglobulinemia, fixed drug eruption, pyoderma gangrenosum, brown recluse spider bite.
Clinical diagnosis is based on morphologic features of lesion and the clinical setting, i.e., underlying diseases, travel history, animal exposure, history of bite, and age. Confirmed by culture in only 29% of cases in immunocompetent patients. Suspicion of necrotizing fasciitis requires immediate deep biopsy and frozen-section histopathology.
With timely diagnosis and treatment, soft-tissue infection resolves with oral or parenteral antibiotic treatment.
Dissemination of infection (lymphatics, hematogenously) with metastatic sites of infection occurs if effective treatment is delayed. In immunocompromised patients, prognosis depends on prompt restoration of altered immunity, usually on correction of neutropenia. Without surgical debridement, necrotizing fasciitis is fatal.
Systemic high dose antibiotic treatment according to type and sensitivity of microbial organism.
Necrotizing Soft-Tissue Infections
Characterized by rapid progression of infection with extensive necrosis of soft tissues and overlying skin. Necrotizing fasciitis.
Etiology. Caused by beta-hemolytic GAS. Less commonly, groups B, C, or G. Necrotizing soft-tissue infections also caused by P. aeruginosa, Clostridium species, mixed infection with anaerobes.
Portal of Entry. May begin deep at site of nonpenetrating minor trauma (bruise, muscle strain). Minor trauma, laceration, needle puncture, or surgical incision on an extremity. GAS may be seeded to this site during transient bacteremia. Clinical variants of necrotizing soft-tissue infection differ with causative organism, anatomic location of infection, underlying conditions. Streptococcal necrotizing myositis occurs as a primary myositis. Streptococcal TSS may occur with GAS necrotizing fasciitis. GBS causes necrotizing fasciitis in episiotomy incisions.
Diagnosis. Imperative in understanding pathogenesis and deciding on the appropriate antimicrobial and surgical therapies.
When skin necrosis is not obvious, diagnosis must be suspected if there are signs of severe sepsis and/or some of the following local symptoms/signs: severe spontaneous pain, indurated edema, bullae, cyanosis, skin pallor, skin hypesthesia, crepitation, muscle weakness, foul smelling exudates.
Local redness, edema, warmth, pain in the involved site, typically on an extremity.
Characteristic findings appear within 36-72 h after onset: involved soft tissue becomes dusky blue in color; vesicles or bullae appear. Infection spreads rapidly along fascial planes (Fig. 25-31). Extensive, cutaneous soft-tissue necrosis develops. Involved tissue may be anesthetic. Necrosis manifests as a black eschar with surrounding irregular border of erythema. Fever and other constitutional symptoms are prominent as the inflammatory process extends rapidly over the next few days. Streptococcal TSS occurs with GAS, GBS, GCS, GGS. Metastatic abscesses may occur as a consequence of bacteremia. Secondary thrombophlebitis occurs.
Figure 25-31. Necrotizing fasciitis of buttock Black eschar within an erythematous, edematous plaque involving the entire buttock with rapidly progressive area of necrosis. GAS, GBS, GCS, GGS. Metastatic abscesses may occur as a consequence of bacteremia. Secondary thrombophlebitis occurs.
Pyoderma gangrenosum, calciphylaxis, ischemic necrosis, warfarin necrosis, pressure ulcer, brown recluse spider bite.
Surgical Debridement. Requires early and complete surgical debridement of necrotic tissue in combination with high-dose antimicrobial agents.
Lymphangitis ICD-9: 457-2 ICD-10: 189-1
An inflammatory process involving the subcutaneous lymphatic channels.
Acute lymphangitis: GAS; S. aureus; other bacteria. Herpes simplex virus.
Subacute to chronic nodular lymphangitis: Mycobacterium marinum, other NTM, Sporotrix schenkii, N. brasiliensis.
Acute Lymphangitis. Portal of entry: Break in skin, wound, S. aureus paronychia, primary herpes simplex infection. Pain and/or erythema proximal to break in skin. Red linear streaks and palpable lymphatic cords, up to several centimeters in width, extend from the local lesion toward the regional lymph nodes (Fig. 25-32), which are usually enlarged and tender.
Figure 25-32. Acute lymphangitis of forearm: S. aureus A small area of the cellulitis on the volar wrist with a tender linear streak extending proximally up the arm; the infection spreads from the portal of entry within the superficial lymphatic vessels.
Subacute and chronic lymphangitis; nodular lymphangitis; see discussion on Nocardiosis, NTM infection, and sporotrichosis.
Linear Lesions on Extremities. Phyto-allergic contact dermatitis (poison ivy or oak), phytophotodermatitis, superficial thrombophlebitis.
Nodular Lymphangitis. M. marinum, N. brasiliensis, S. schenckii infection.
The combination of an acute peripheral lesion with proximal tender/painful red linear streaks leading toward regional lymph nodes is diagnostic of lymphangitis. Isolate S. aureus or GAS from portal of entry.
Resolves with correct diagnosis and treatment. Bacteremia with metastatic infection in various organs uncommon with adequate treatment.
Systemic antibiotic depending on causative organism.
Wound. Injury in which skin is surgically incised or traumatically injured (open wound) or in which blunt force trauma causes a contusion (closed wound). Wound infection: Skin and all wounds are colonized by bacteria and other microbes, i.e., cutaneous microbiome. Infection is characterized by pain, tenderness, purulence, erythema, warmth, and must be diagnosed on clinical as well as culture findings.
Etiology and Epidemiology
Classification. Traumatic wounds: Open or closed wounds (Fig. 25-33). Surgical wounds: Infection in surgical incisions (Fig. 25-34). Burn wounds: Burn wound may become superficially colonized with S. aureus; open burn-related surgical wound infection; burn wound cellulitis; invasive infection in debrided burn wounds (Fig. 25-35). Chronic ulcers: Arterial insufficiency; venous insufficiency; neuropathic ulcers/diabetes mellitus; pressure ulcers (bedsores) (Figs. 25-36 to 25-38). Bites: Animal; human; insect.
Figure 25-33. Laceration infection in renal transplant recipient: MRSA 60-year-old male immunosuppressed renal transplant recipient was unaware of a laceration on the calf. Erythema and induration are seen around the crusted wound. MRSA was isolated on culture. Two circled invasive squamous cell carcinomas are also seen on the calf.
Figure 25-34. Surgical excision wound infection: MSSA Surgical wound became painful and tender 7 days after excision of squamous cell carcinoma; soft tissue (cellulitis) is seen adjacent to the wound margin. Necrotic tissue is seen in the base.
Figure 25-35. Burn wound infection: MSSA 10-year-old male with extensive third degree thermal burn treated with autologous skin grafting has extensive new crusted erosions. MSSA was cultured from the infected site.
Figure 25-36. Wound infection of stasis ulcer 75-year-old female with varicose veins and enlarging stasis ulcer infected with MRSA and Pseudomonas aeruginosa. IV antibiotics were administered. Incompetent veins were treated with endovascular laser ablation. The ulcer healed with minimal scar.
Figure 25-37. Infection of diabetic ulcer: MRSA 86-year-old male with diabetes mellitus type 2 had a chronic neuropathic ulcer on the R-lateral foot. The ulcer rapidly enlarged associated with fever and glucose of 450 mg/dL. MSSA was isolated from the wound. He was hospitalized and treated with IV antibiotics. He died 3 months later.
Figure 25-38. Wound infection and cellulitis: MRSA 53-year-old male with obsessive-compulsive disorder excoriates extremities in the evening. MRSA infection has occurred repeatedly. Ulcers resolved with doxycycline, doxepin, and unna boots applied weekly.
Epidemiology. S. aureus in the most common pathogen in wound infections, MSSA and increasingly MRSA. Surgical wound infection is up to 10 times more likely among patients who harbor S. aureus in nares. Hospital-acquired (nosocomial) or health-care-associated infections (most commonly surgical wound infections) are the most common complication affecting hospitalized patients.
Pathogenesis. Wounds are initially colonized by skin flora or introduced organisms. In some cases, these organisms proliferate, causing a host inflammatory response defined as infection.
Local Infection. Tenderness of wound area, erythema, hot, purulent drainage, induration. Invasive infection: malaise, anorexia, sweats, fever, chills. Sepsis syndrome: fever, hypotension. Types of Surgical Infections. Superficial infection of wound, wound infection with soft-tissue infection, i.e., cellulitis and erysipelas, soft-tissue abscess, necrotizing soft-tissue infection, tetanus.
Allergic contact dermatitis (e.g., neomycin), pyoderma gangrenosum, vasculitis.
Because all open wounds are colonized with microorganisms, diagnosis of infection relies on the clinical characteristics of the wound. Wound culture identifies the potential pathogen(s).
Although all wounds require treatment, only infected lesions require antimicrobial therapy.
Disorders Caused by Toxin-Producing Bacteria
Bacteria colonize skin and mucosa (mucocutanous microbiome), replicate locally, and elaborate toxins that cause local mucocutaneous and systemic disorders.
Clinical syndromes caused by these toxins:
Bullous impetigo (see Figs. 25-12 and 25-13).
Staphylococcal scalded-skin syndrome. Generalized form with extensive epidermolysis, followed by desquamation (Figs. 25-39 and 25-40).
TSS. Abortive form, staphylococcal scarlet fever.
Bacillus anthracis: Anthrax
Corynebacterium diphtheriae: Diphtheria
Clostridium tetani: Tetanus
Staphylococcal Scalded-Skin Syndrome
ICD-9: 695.81 ICD-10: L00
Etiology. S. aureus producing exfoliative toxins. Occurs in neonates and young children.
Pathogenesis. Illness develops after toxin synthesis and absorption and the subsequent toxin-initiated host response. Exotoxins cleave desmoglein-1 in epidermal granular cell-layer desmosomes that link adjoining cells. Exotoxins are proteases that cleave desmoglein-1, which normally hold the granulosum and spinulosum layers together. Antitoxin antibodies are protective against SSSS and TSS.
Localized Form. See “Bullous Impetigo” in Figs. 25-12 and 25-13. Intact flaccid purulent bullae, clustered. Rupture of the bullae results in moist red and/or crusted erosive lesions. Lesions are often clustered in an intertriginous area.
Generalized Form. Exfoliative toxin-induced changes: macular scarlatiniform rash (staphylococcal scarlet fever syndrome) or diffuse, ill-defined erythema and a fine, stippled, sandpaper appearance occur initially. In 24 h, erythema deepens and involved skin becomes tender. Initially, periorificially on face, neck, axillae, groins; becoming more widespread in 24-48 h. Superficial epidermis is most pronounced periorificially on face; in flexural areas on neck, axillae, groins, antecubital areas; back (pressure points). With epidermolysis, epidermis appears wrinkled and can be removed by gentle pressure (skin resembles wet tissue paper) (Nikolsky sign) (Fig. 25-39). In some infants, flaccid bullae occur. Unroofed epidermis forms erosions with red, moist base (Fig. 25-39). Desquamation occurs with healing (Fig. 25-40).
Figure 25-39. Staphylococcal scalded-skin syndrome: Nikolsky sign The skin of this infant is diffusely erythematous; gentle pressure to the skin of the arm has sheared off the epidermis, which folds like tissue paper.
Figure 25-40. Staphylococcal scalded-skin syndrome: sloughing and desquamation in this infant, painful, tender, diffuse erythema was followed by generalized epidermal sloughing and erosions. S. aureushad colonized the nares with perioral impetigo, the site of exotoxin production. (A) Extensive desquamation is seen on buttocks and legs (B).
Mucous membrane, uninvolved. TSS, in comparison, manifests with mucosal erythema.
Kawasaki syndrome, adverse cutaneous drug eruption, scarlet fever.
Clinical findings confirmed by bacterial cultures.
With adequate antibiotic treatment, superficially denuded areas heal in 3-5 days associated with generalized desquamation; there is no scarring.
Systemic antibiotic to treat infection and stop toxin production.
Toxic Shock Syndrome ICD-9: 040.82 ICD-10: A48.3
Etiology. Exotoxin (TSST-1)-producing S. aureus; less commonly GAS.
Menstrual TSS (MTSS)
Nonmenstrual TSS (NMTSS) occurs secondary to a wide variety of primary and secondary S. aureus infections of underlying dermatoses.
Streptococcal TSS. Skin or soft-tissue infection with toxin production.
Rapid onset of fever, intractable hypotension, multisystem failure. Rash.
Generalized scarlatiniform erythroderma, most intense around infected area. Blanching erythema, “painless sunburn.” Fades within 3 days of appearance. Edema. Mucous membranes: Erythema. Ulcers: mouth, esophagus, vagina. Desquamation. Begins 1 week after the onset of skin lesions: skin of torso, face, and extremities, followed by desquamation of palms, soles, fingers/toes.
Mucous Membranes. Eyes: Intense erythema and injection of bulbar conjunctivae. Subconjunctival hemorrhages. Mouth: Erythema of mucous membranes of mouth, tongue, pharynx, tympanic membranes. Strawberry tongue. Ulcers: mouth, esophagus.
Genital: vagina erythema, ulcers.
General Findings. Fever. Organ hypoperfusion results in renal and myocardial dysfunction, fluid overload, and adult respiratory distress syndrome. Late complications include peripheral gangrene, muscle weakness, lingering asthenia, neuropsychiatric dysfunction.
Streptococcal TSS 25-50% mortality. NMTSS 6.4% mortality; MTSS 2.5% mortality.
Systemic antibiotic to treat infection and stop toxin production. Supportive.
Scarlet Fever ICD-9: 034 ICD-10: A38
Group A β-hemolytic streptococcus (GAS) (S. pyogenes), erythrogenic toxin-producing strains.
Exfoliative toxin (E1)-producing S. aureus.
Infection. Pharyngitis; tonsillitis. Infected surgical or other wound; secondarily infected dermatoses.
Toxin Syndrome (Scarlet Fever). Patient may appear acutely ill with high fever, fatigue, sore throat, headache, nausea, vomiting, tachycardia. Anterior cervical lymphadenitis associated with pharyngitis/tonsillitis. Scarlatiniform exanthema occurs in nonimmune persons.
Exanthem. Face flushed with perioral pallor. Finely punctate erythema is first noted on the upper part of the trunk (Fig. 25-41); may be accentuated in skin folds such as neck, axillae, groin, antecubital, and popliteal fossae; linear petechiae (Pastia sign) occur in body folds. Palms/soles usually spared.
Figure 25-41. Scarlet fever: exanthem Finely punctated erythema has become confluent (scarlatiniform); petechiae can occur and have a linear configuration within the exanthem in body folds (Pastia line).
Initial punctate lesions become confluently erythematous, i.e., scarlatiniform. Intensity of the exanthem varies from mild to moderate erythema confined to the trunk due to an extensive purpuric eruption.
Exanthem fades within 4-5 days and is followed by desquamation on the body and extremities and by sheetlike exfoliation on the palms/fingers and soles/toes. In subclinical or mild infections, exanthem and pharyngitis may pass unnoticed. In this case, patient may seek medical advice only when exfoliation on the hand and soles is noted.
Enanthem. Pharynx beefy red. Forchheimer spots: Small red macules on hard/soft palate, uvula. Punctate erythema and petechiae may occur in the palate. White tongue: Initially is white with scattered red, swollen papillae (white strawberry tongue) (Fig. 25-42). Red strawberry tongue: By the fourth or fifth day, the hyperkeratotic membrane is sloughed, and the lingular mucosa appears bright red (Fig. 25-42).
Figure 25-42. Scarlet fever: white and red strawberry tongue The white patches at the back of the tongue represent residua of the initial white strawberry tongue.
Nonsuppurative Sequelae. Acute rheumatic fever: Onset 1-4 weeks after onset of pharyngitis. Incidence of acute rheumatic fever has markedly decreased during the past five decades.
Acute glomerulonephritis: More common after impetigo with nephritogenic strain of GAS (types 4, 12, 2, 49, and 60).
Guttate psoriasis (see Section 3).
Erythema nodosum may follow if the infection goes untreated (see Section 7).
Viral exanthema, adverse cutaneous drug eruption, Kawasaki syndrome, infectious mono-nucleosis.
Rapid direct antigen tests: used to detect GAS antigens in throat swab specimens. Isolate GAS on culture of specimen from throat or wound. Blood cultures are rarely positive. Centor criteria for diagnosis of acute streptococcal pharyngitis: History of fever; tonsillar exudates; tender anterior cervical adenopathy; absence of cough.
Systemic antibiotic to treat infection and prevent nonsuppurative sequelae. Systemic penicillin is the drug of choice, alternatives are erythromycin, azathioprin, clarithromycin or cephalosporins.
Cutaneous Anthrax ICD-9: 022 ICD-10: A22
Etiology. B. anthracis, a nonmotile, gram-positive, aerobic rod. Zoonosis. Spores can remain dormant in soil for decades. Low-level germination occurs at the primary site, resulting in local edema and necrosis. Primary infection: skin, pulmonary, GI. Pathogenesis: toxin mediated.
Transmission. Zoonosis of mammals, especially herbivores. Human infections result from contact with contaminated wild and domestic animals or animal products. Human-to-human transmission does not occur. Bioterrorism (2001). At risk: farmers, herders; slaughterhouse, textile workers.
Cutaneous anthrax. Accounts for 95% of anthrax cases in the United States.
Cut or abrasion on exposed sites of head, neck, extremities. Nondescript, painless, pruritic papule (resembling insect bite) appears 3-5 days after introduction of endospores. In 1-2 days, evolves to vesicle(s) ± hemorrhage + necrosis. Vesicles rupture to form ulcers with extensive local edema (Fig. 25-43), ultimately forming dry eschars (1-3 cm).
Figure 25-43. A cutaneous anthrax A 40-year-old farmer with anthrax. (A) A black eschar at the site of inoculation with a central hemorrhagic ulceration on the thumb associated with massive edema of the hand. (B) A nodular lymphangitis extending proximally from the primary lesion on the thumb.
Satellite lesions can form in a nodular lymphangitis proximally on edematous extremity (Fig. 25-43).
Edema: More extensive on head/neck.
Ecthyma, brown recluse spider bite, ulceroglandular tularemia, orf, glanders.
Isolation of B. anthracis from skin lesions, blood, or respiratory secretions or by measuring specific antibodies in blood of persons with suspected symptoms.
Course and Treatment
Mortality rate in untreated persons with cutaneous anthrax is about 20%. Systemic penicillin is the drug of choice, alternatives are erythromycin, azathioprin, clarithromycin or cephalosporins.
Cutaneous Diphtheria ICD-9: 032 ICD-10: A30
Etiology. Corynebacterium diphtheria. Cases in industrialized countries extremely rare.
Pathogenesis. Localized infection caused by toxigenic and nontoxigenic strains. Acute infection may involve any mucous membrane or skin wound. Toxin causes myocarditis and peripheral neuropathy.
Cutaneous Diphtheria. Nonspecific wound.
Pharynx. Tenacious gray membrane at the portal of entry in pharynx. Respiratory diphtheria is usually caused by toxicogenic (tox+) strains.
Myocarditis. Arrhythmias, heart block, and heart failure.
Polyneuritis. Neuropathy usually involves cranial nerves first: diplopia, slurred speech, and difficulty in swallowing.
Made by isolation of C. diphtheria on culture of wound.
Penicillin, erythromycin, antitoxin.
Vaccination. Immunity to vaccine wanes over time. Decennial boosters are recommended.
Tetanus ICD-9: 037 ICD-10: A33
Etiology. C. tetani. Spores survive in soil for years. Spores germinate in wounds with low oxidation–reduction potential (devitalized tissue, foreign bodies, or active infection).
Pathogenesis. C. tetani releases a powerful neurotoxin causing increased muscle tone and spasms (lockjaW).
Demography. Tetanus affects nonimmunized persons, partially immunized persons, or fully immunized individuals who fail to maintain adequate immunity with booster doses of vaccine. At risk: elderly, newborns, migrant workers, injecting drug users. Activities: farming, gardening, and other outdoor activities. Without immunization, tetanus occurs predominantly in neonates and other young children.
Follows inoculation of spores into skin. Incubation period is 5 days to 15 weeks; average 8-12 days.
Site of Infection: Minor traumatic wound: puncture wound, laceration, abrasion.
Secondary Infection: Injecting drug use (“skin popping”), skin ulcers, gangrene, frostbite, burns, surgical wounds, childbirth, abortion; abscesses, middle-ear infection.
Tetanus. Begins with mild spasms in the jaw muscles, i.e., lockjaw. Spasms can also affect the chest, neck, back, and abdominal muscles. Back muscle spasms often cause arching, called opisthotonos (Fig. 25-44). Sometimes, the spasms affect muscles of respiration. Tetany: Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups; can cause fractures and muscle tears. Other symptoms: drooling, hyperhidrosis, fever, hand or foot spasms, irritability, swallowing difficulty, uncontrolled urination or defecation.
Figure 25-44. Muscular spasms (specifically opisthotonos) in a patient suffering from tetanus. Painting by Sir Charles Bell, 1809.
Provide supportive care, including wound care. Antibiotics, antitoxin. Magnesium sulfate and beta-blockers may be used to manage muscle spasms and cardiac problems.
Cutaneous Nocardia Infections
Etiology. Nocardia species of bacteria. Saprophytic gram-positive anaerobic actinomycetes living in soil. Actinomyces were mistakenly classified as fungi. N. brasiliensis is usually associated with disease limited to the skin. Infection follows traumatic inoculation into the skin on extremity.
Cellulitis. Inflammation 1-3 weeks following traumatic inoculation. Expanding erythema, induration; firm, nonfluctuant. Untreated, infection can progress to involve adjacent muscles, tendons, bones, joints. Dissemination is rare.
Nodular Lymphangitis. Begins as nodule at inoculation site. Untreated, infection extends into lymphatic vessels with linear subcutaneous nodules.
Cutaneous Nocardiosis. Nodule occurs at the site of inoculation (Fig. 25-45), most commonly feet or hands. Untreated, infection expands forming plaques with sinus tracts and fistula formation (Fig. 25-46). As with eumycetoma, grains (dense masses of bacterial filaments extending radially from a central core) may be seen in discharging pus and tissue. After years, deformity of extremity may occur with involvement of adjacent anatomical structure.
Figure 25-45. Cutaneous nocardiosis A 23-yearold female from Central America with a painful lesion for 6 months. Confluent erythematous violaceous nodules on the right prepatellar area arising in an abrasion. Nocardia brasiliensis isolated on culture of biopsy specimen. The lesion resolved with trimethoprim-sulfamethoxazole.
Figure 25-46. Chronic cutaneous nocardiasis Swelling, multiple sinus tracts, and involvement of the foot. (Image provided by Amor Khachemoune and Ronald O. Perelman, New York University School of Medicine.)
Disseminated Nocardiosis with skin Involvement. Most cases occur in people with host defense defects.
Grains and organism in purulent discharge or in histologic specimens. Isolate and speciate Nocardia in pus, exudate, or tissue. Sensitivities determined on isolated organism.
Nodular Lymphangitis. Sporotrichosis, NTM infection.
Tends to relapse, especially with defective host defenses.
Combination of sulfamethoxazole and trimethoprim may be more effective than a sulfonamide alone. Minocycline 100 mg BID.
Rickettsiae. Gram-negative bacteria. Coccobacilli/short bacilli; obligate localization/persistence within eukaryotic cells.
Transmitted to humans by arthropods; tick, mite, flea, louse; mammalian reservoirs; humans are incidental hosts.
Rickettsial Disorders. Spotted fever group, typhus group, scrub typhus group.
Exposure to vectors or animal reservoirs, travel to or residence in endemic locations (http://www.cdc.gov/ncidod/diseases/submenus/sub_typhus.htm)
Tâche noire (black spot or stain). Coin-like lesion with central eschar and red halo at site of vector-feeding bite site.
Exanthem. Macules-papules. Exception: rickettsialpox with papules-vesicles.
Later Findings Varying with Pathogen. may become hemorrhagic with vasculitis.
Confirmed by paired serum samples after convalescence or demonstration of rickettsiae.
Dermatopathology. Rickettsiae multiply in endothelial cells of small blood vessels and produce vasculitis with necrosis and thrombosis.
Rickettsiae can cause life-threatening infections. Order of decreasing case-fatality rate: R. rickettsii [Rocky Mountain spotted fever (RMSF)]; R. prowazekii (epidemic louseborne typhus); Orientia tsutsugamushi (scrub typhus); R. conorii (Mediterranean spotted fever); R. typhi (endemic murine typhus); in rare cases, other spotted fever group organisms.
Doxycycline is the drug of choice, 100 mg BID orally. Alternates: ciprofloxacin, chloramphenicol.
Tick Spotted Fevers ICD-9: 082.9 ICD-10: A77.0
Characteristic exanthema: macules and papules.
RMSF R. rickettsia
Tick typhus Boutonneuse R. conorii. Siberian tick typhus R. sibirica, Australian tick typhus R. autralis, Oriental spotter fever R. japonica, African tick bite fever R. africae, etc.
Rickettsialpox R. akari
Transmission. Vector Various ixodes ticks. Worldwide distribution. Rickettsiae are transmitted by tiny immature larvae and nymphs; often attachment unnoticed.
Inoculation. Bite; excoriation of feeding site inoculates rickettsiae in tick body fluid or feces. Travel history. Recent travel to or living in endemic region, e.g., recent African safari, adventure travel, military service in Africa with African tick bite fever.
Incubation period: average 7 days after tick bite. Onset sudden of symptoms in 50% of patients. Most common: headache, fever; also chills, myalgias, arthralgias, malaise, anorexia.
Tâche noire at inoculation site. An inoculation eschar: papule forms at the bite site and evolves to a painless, black-crusted ulcer with red halo (Fig. 25-47) in 3-7 days. Occurs in all spotted fevers except RMSF.
Figure 25-47. African spotted fever: tache noir 65-year-old female, who had recently returned from trip to South Africa, noted a lesions on the thigh (A) and reported flu-like symptoms. A central dark crust (tache noir) (B) with halo of erythema is seen at the site of tick bite. Paired serologies confirmed the diagnosis of African spotted fever. Symptoms resolved with doxycycline.
Exanthem. About 3-4 days after appearance of tâche noire, an erythematous macules and papules appear on trunk; may subsequently disseminate, involving face, extremities, palms/soles. Density of eruption heightens during next few days. In severe cases, lesions may become hemorrhagic.
Distribution. Similar pattern of spread and distribution in all spotted fevers—trunk, extremities, face (centrifugal)—except RMSF, which first appears at wrists and ankles and spreads centripetally.
Systemic Findings. Conjunctivitis, pharyngitis, photophobia. Central nervous system (CNS) symptoms: confusion, stupor, delirium, seizures, coma; common in RMSF but not seen in other spotted fevers.
Viral exanthems, drug eruption, vasculitis.
Rocky Mountain Spotted Fever ICD-9: 082.0 ICD-10: A77
Etiology. Rickettsia rickettsii.
Transmission. ‘Bite’ of infected tick; only 60% of patients aware prior tick bite. Most common in springtime in the southeastern United States; four states (North Carolina, Oklahoma, Tennessee, South Carolina) account for 48% of US cases; 600 reported cases of RMSF in the United States annually.
Abrupt onset of symptoms. Fever, chills, shaking rigor. Anorexia, nausea, vomiting. Malaise, irritability. Severe headache. Myalgia. Can mimic acute abdomen, acute cholecystitis, acute appendicitis. Tâche noire uncommon in RMSF.
Early exanthem: 2-6 mm, pink, blanchable macules (Figs. 25-48 and 25-49). In 1-3 days, evolve to deep red papules (Fig. 25-50). Characteristically, rash begins on wrists, forearms, and ankles and somewhat later on palms and soles. Within 6-18 h, rash spreads centripetally to the arms, thighs, trunk, and face.
Figure 25-48. Rocky Mountain spotted fever: early Erythematous macules and papules appeared initially on the wrists of a young child. The lesions are not completely blanchable with pressure, indicating early hemorrhage of dermal blood vessels.
Figure 25-49. Rocky Mountain spotted fever: early Erythematous and hemorrhagic macules and papules appeared initially on the ankles of an adolescent.
Figure 25-50. Rocky Mountain spotted fever: late Disseminated hemorrhagic macules and papules on the face, neck, trunk, and arms on the fourth day of febrile illness in an older child. The initial lesions were noted on the wrists and ankles, subsequently extending centripetally.
Later exanthem: In 2-4 days, become hemorrhagic, no longer blanchable. Local edema. Hemorrhagic rash may occur on palms and soles. Necrosis occurs in acral extremities following prolonged hypotension.
Spotless fever: 13% of cases. Associated with higher mortality rate because of delay in diagnosis.
Clinical and epidemiologic considerations more important than a laboratory diagnosis in early RMSF. Suspect in febrile children, adolescents, and men >60 years of age with tick exposure in endemic areas. Diagnosis made clinically and confirmed later. Only 3% of patients with RMSF present with the triad of rash, fever, and history of tick bite during the first 3 days of illness.
Clinical, epidemiologic, and convalescent serologic data establish the diagnosis of a spotted fever-group rickettsiosis.
In France and Spain, mortality rate is similar to that of RMSF. Spotted fevers are usually milder in children. Morbidity and mortality rates are higher (up to 50%) in individuals with diabetes mellitus, cardiac insufficiency, alcoholism.
Severe course is associated with older age, delay in diagnosis, delay in or no treatment and is more common in men, individuals of African descent, and those with alcoholism or G6PD deficiency. Fatality rate: 1.5% with known tick bite but 6.6% if no known tick exposure. Fulminant RMSF defined as a fatal disease whose course is unusually rapid (i.e., 5 days from onset to death) and usually characterized by early onset of neurologic signs and late or absent rash. In uncomplicated cases, defervescence usually occurs within 48-72 h after initiation of therapy.
Rickettsialpox ICD-9: 083.2 ICD-10: A79.1
Epidemiology. R. akari. Vector: mice mite (Liponyssoides sanguineus), other mites; transovarian transmission. Geography: United States, Europe, Russia, South Africa, Korea, Europe
Tâche noire (Fig. 25-51). At tick bite site.
Figure 25-51. Rickettsialpox: tâche noire. A crusted, ulcerated papule (eschar) with a red halo resembling a cigarette burn at the site of a tick bite.
Exanthem. 2-6 days after the onset of nonspecific symptoms, red macules and papules appear. May evolve to characteristic vesicles (pox); crusted erosions occur. Lesions usually heal without scarring.
Fever resolves in 6-10 days without treatment with doxycycline.
Viral exanthems, varicella, pityriasis lichenoides et varioliformis acuta.
Infective Endocarditis ICD-9: 421 ICD-10: 133
Inflammation of endocardium. Infective and noninfective. Usually of heart valve. Characterized by vegetations that are made up of fibrin, platelets, inflammatory cells (and microcolonies of microorganism if infective endocarditis.
Infective endocarditis. Occurs at sites on altered endothelium or endocardium. The primary event is bacterial adherence to damaged valves during transient bacteremia. Bacteria grow within the cardiac lesion(s), i.e., vegetations, with local extension and cardiac damage. Subsequently, septic embolization occurs to skin, kidney, spleen, brain, etc. Circulating immune complexes may result in glomerulonephritis, arthritis, or various mucocutaneous manifestations of vasculitis. Embolization of vegetative fragments results in infection/infarction of remote tissues.
Acute bacterial endocarditis rapidly damages cardiac structures, hematogenously seeds extracardiac sites, may progress to death in a few weeks.
Subacute bacterial endocarditis (SBE) causes structural damage slowly, rarely causes metastatic infection, and is gradually progressive unless complicated by a major embolic event or ruptured mycotic aneurysm.
Noninfective endocarditis: Occurs on previously undamaged valves. Hypercoagulable state. Murantic endocarditis. Libman-Sacks endocarditis.
Diagnosis: Based on clinical features, echocardiogram, blood cultures.
Septic Arterial Emboli. Common with acute S. aureus endocarditis. Hematogenously seeded focal infection (Fig. 25-52). Apparent in up to 50% of patients.
Figure 25-52. Septic vasculitis associated with bacteremia Dermal nodule with hemorrhage and necrosis on the dorsum of a finger. This type of lesion occurs with bacteremia (e.g., S. aureus, gonococcus) and fungemia (e.g., Candida tropicalis).
Osler Nodes. Painful, erythematous nodules most commonly found on the pads of the fingers and toes of some patients with infective endocarditis.
Janeway Lesions. Nontender, erythematous, and nodular lesions most commonly found on the palms and soles (Fig. 25-53) of some patients with infective endocarditis.
Figure 25-53. Infective endocarditis, acute: Janeway lesions Hemorrhagic, infarcted papules on the volar fingers in a patient with S. aureus endocarditis.
Splinter Hemorrhages. A small linear longitudinal subungual hemorrhage, initially red then brown. Middle third of nail bed in SBE.
Petechial Lesions. Small, nonblanching, reddish-brown macules. Occur on extremities, upper chest, mucous membranes [conjunctivae (Fig. 25-54), palate]. Occur in crops. Fade after a few days (20-40%).
Figure 25-54. Infective endocarditis, acute: subconjunctival hemorrhage Submucosal hemorrhage of the lower eyelid in an elderly diabetic with enterococcal endocarditis; splinter hemorrhages in the midportion of the nail bed and Janeway lesions were also present on the volar fingers. Infection followed urosepsis.
Roth Spots. White spot in the retina close to the optic disk, often surrounded by hemorrhages; also seen in pernicious anemia, leukemia.
Septic Embolism. Painful, hemorrhagic macules, papules, or nodules, usually acral location.
Course and Treatment
Varies with underlying cardiac disease and baseline health of the patient, as well as with the complications that occur. Complications: congestive heart failure, stroke, other systemic embolizations, septic pulmonary embolization. Aortic valve involvement has higher risk of death or need for surgery Antibiotics.
Sepsis ICD-9: 995.91 ICD: A40
Sepsis is a whole-body inflammatory state, in response to infection. Severe sepsis occurs complicated by multiple organ dysfunction syndrome. Septicemia occurs with pathogenic microbe in blood resulting in sepsis.
Characterized by fever or hypothermia, tachypnea, tachycardia, and, in severe cases, multiple organ dysfunction syndrome.
Epidemiology. 750,000 cases in the United States annually; >200,000 deaths. Two-thirds of cases occur in persons hospitalized for other illnesses. Incidence is increasing. Risk factors: Increasing age, preexisting comorbidities, use of antibiotics, host defense defects, venous access lines, mechanical ventilation.
Cutaneous infections as source of sepsis: superficial skin infections, soft-tissue infections, wounds. E. gangrenosum (Fig. 25-29): P. aeruginosa most commonly.
Exanthem. See meningococcemia and RMSF (Fig. 25-48).
Petechiae. Cutaneous/oropharyngeal location suggests meningococcal infection; less commonly, H. influenzae. In patient with tick bite living in endemic area, RMSF (Fig. 25-50).
Hemorrhagic Bullous Lesions. V. vulnificus in patient (diabetes mellitus, liver disease) with history of eating raw oysters or clams (Fig. 25-30).
Disseminated intravascular coagulation. See Section 20. (Fig. 20-3)
Severe prolonged hypotension with acral necrosis of fingers/hands and feet (Figs. 25-52 and Fig. 25-55).
Figure 25-55. Septic shock: ischemic necrosis of acral sites Capnocytophaga canimorsus sepsis (dog bite) with prolonged hypotension and hypoperfusion resulted in infarction of fingers and nose.
Course and Treatment
Early sepsis is reversible; septic shock has high morbidity. High dose antibiotics plus treatment of disseminated intravascular coagulation.
Meningococcal Infection ICD-9: 036.9 ICD-10: A39
Etiology. N. meningitidis, colonizes nasopharynx. Infects only humans; no animal reservoirs. Spread by persons-to-person contact through respiratory droplets.
Demography. The disease occurs sporadically throughout the world. The highest burden of the disease is due to the cyclic epidemics occurring in the African meningitis belt.
Small pink blanchable macules and papules occur soon after onset of disease (Fig. 25-56). With vascular friability and hemorrhage, petechiae and ecchymoses occur; first seen on ankles, wrists, axillae, mucosal surfaces, and conjunctivae. A cluster of petechiae may be seen at pressure points—e.g., where a blood pressure cuff has been inflated. Ecchymoses and purpura may progress to hemorrhagic bullae, undergo necrosis, and ulcerate. Confluent necrotic hemorrhagic lesions may have bizarre-shaped, grayish to black necrosis, i.e., purpura fulminans) associated with disseminated intravascular coagulation (DIC) in fulminant disease (Fig. 25-57).
Figure 25-56. Acute meningococcemia: early exanthem Discrete, pink-to-purple macules and papules as well as purpura on the face of this young child. These lesions represent early disseminated intravascular coagulation with its cutaneous manifestation, purpura fulminans.
Figure 25-57. Acute meningococcemia: purpura fulminans Maplike, gray-to-black areas of cutaneous infarction of the leg in a child with NM meningitis and disseminated intravascular coagulation with purpura fulminans.
Meningococcemia Septicemia. Meningococci enter the bloodstream and multiply, damaging the walls of the blood vessels and causing bleeding into the skin and organs. Characterized by development of shock and multiorgan failure. Peripheral gangrene may occur, requiring amputation in those who survive.
Waterhouse-Friderichsen Syndrome. Fulminant meningococcal septicemia characterized by high fever, shock, widespread purpura, disseminated intravascular coagulation, thrombo-cytopenia, and adrenal insufficiency.
Meningococcal Meningitis. Bacteremia can result in the seeding of many organs, especially the meninges. The symptoms of meningococcal meningitis are those of typical bacterial meningitis, namely, fever, headache, stiff neck, and polymorphonuclear neutrophils (PMNs) in spinal fluid.
Chronic Meningococcemia. Intermittent bacteremia. Slow replication seeds various organs: meninges, pericardium, large joints, skin. Host inflammatory reaction limited to seeded site.
Adverse cutaneous drug eruptions, vasculitis, RMSF, infective endocarditis.
Definitive etiologic diagnosis requires isolation of meningococci from blood or local site of infection.
Onset of symptoms is sudden and death can follow within hours. In as many as 10-15% of survivors, there are persistent neurological defects, including hearing loss, speech disorders, loss of limbs, mental retardation, and paralysis.
Etiology. Bartonella spp.; tiny gram-negative bacilli that can adhere to and invade mammalian cells such as endothelial cells and erythrocytes.
Transmission. Cat scratch or bite. Body louse or sandfly bite.
Vary with the immune status of the host.
Bartonella Henselae. Immunocompetent host: cat-scratch disease. HIV disease: bacillary angiomatosis.
B. Bacilliformis. Nonimmune, nonresidents of endemic area: Oroya fever with severe febrile illness, profound anemia. With immunity after convalescence: verruga peruana with red-purple cutaneous lesions (Peruvian warts; resemble angiomatous lesions of bacillary angiomatosis).
High dose antibiotic therapy and treatment of DIC.
Prophylaxis. Several vaccines are available to control the disease.
B. Quintana. Trench fever presenting as a febrile systemic illness with prolonged bacteremia; no cutaneous manifestations.
Diseases caused by Bartonella species:
• Cat-scratch disease: B. henselae.
• Bacillary angiomatosis: B. henselae, B. quintana.
• Bacillary peliosis: B. henselae.
• Trench fever: B. quintana.
• Bartonellosis (Carrión disease); Oroya fever and verruga peruana: B. bacilliformis.
Cat-Scratch Disease (CSD) ICD-9: 078.30 ICD-10: A28.1
Etiology. B. henselae. Reservoir: Domestic cat or kittens.
Transmission. Associated with exposure to young cats. Blood cultures of kittens are frequently positive for B. henselae. Cat flea Ctenocephalides felis transmit infection between cats.
Demography/Age of Onset. Majority of cases occur in children.
Pathogenesis. B. henselae causes granulomatous inflammation in healthy individuals (CSD) and angiogenesis in immunocompromised persons.
Inoculation Site. Innocuous-looking, small (0.5-1 cm) papule, vesicle, or pustule; may ulcerate; skin color pink to red; firm, at times tender (Fig. 25-58). Residual linear cat scratch. Persists for 1-3 weeks. Distribution: Exposed skin of face, hands.
Figure 25-58. Bartonellosis: cat-scratch disease with primary lesion Erythematous nodule of the cheek of a 9-year-old girl at the site of cat scratch. Diagnosis was made on the histologic findings of the excised specimen.
Conjunctivae. If portal of entry is the conjunctiva, 3- to 5-mm whitish-yellow granulation on palpebral conjunctiva associated with tender preauricular and/or cervical lymphadenopathy (Parinaud oculoglandular syndrome).
Uncommonly urticaria, transient maculopapular eruption, erythema nodosum.
Regional Lymphadenopathy (Fig. 25-59). Evident within 2-3 weeks after inoculation in 90% of cases; primary lesion, if present, may have resolved by the time lymphadenopathy occurs. Nodes are often solitary, moderately tender, and freely movable. Involved lymph nodes: epitrochlear, axillary, pectoral, cervical. Nodes may suppurate. Usually resolved within 3 months. Generalized lymphadenopathy or involvement of the lymph nodes of more than one region is unusual.
Figure 25-59. Bartonellosis: cat-scratch disease with axillary adenopathy Acute, very tender, axillary lymphadenopathy in a child; cat scratches were present on the dorsum of the ipsilateral hand. (Courtesy of Howard Heller, MD.)
Chancriform syndrome. Suppurative bacterial lymphadenitis, NTM infection, sporotrichosis, tularemia.
Other Cat-Associated Infections. Bite infections caused by P. multocida and C. canimorsus, sporotrichosis; Microsporum canis dermatophytosis.
Suggested by regional lymphadenopathy developing over 2-3 weeks in an individual with cat contact and a primary lesion at the site of contact; confirmed by identification of B. henselae from tissue or serodiagnosis.
Bacillary Angiomatosis ICD-9: 088.0 ICD-10: A44.8
Etiology. B. henselae, B. quintana. Both cause cutaneous angiomas. B. quintana causes subcutaneous nodules and lytic bone lesion.
Demography. Occurs in advanced HIV disease. Incidence decreased with antiretroviral therapy (ART) and prophylaxis of opportunistic infections.
Risk Factors. B. henselae: contact with cats and/or cat fleas (C. felis). B. quintana: low income, homelessness, body louse (P. humanis corporis) infestation.
Papules or nodules resembling angiomas (red, bright red, violaceous, or skin colored) (Fig. 25-60); up to 2-3 cm in diameter; usually situated in dermis with thinning or erosion of overlying epidermis. Larger lesions may ulcerate. Subcutaneous nodules, 1-2 cm in diameter, resembling cysts. Uncommonly, abscess formation. Papules/nodules range from solitary lesions to >100. Firm, nonblanching.
Figure 25-60. Bartonellosis: bacillary angiomatosis 3- to 5-mm cherry hemangioma-like papules and a larger pyogenic granuloma-like nodule on the shin of a male with advanced HIV disease. Subcutaneous nodular lesions were also present. Lesion promptly resolved with oral erythromycin, but required secondary prophylaxis for recurrent lesions.
Distribution. Any site, but palms and soles are usually spared. Occasionally, lesions occur at the site of a cat scratch. A solitary lesion may present as dactylitis.
Mucous Membranes. Angioma-like lesions of lips and oral mucosa. Laryngeal involvement with obstruction.
Systemic Findings. Infection may spread hematogenously or via lymphatics to become systemic, commonly involving the liver (peliosis hepatitis) and spleen. Lesions may also occur in the heart, bone marrow, lymph nodes, muscles, soft tissues, CNS.
Kaposi sarcoma, pyogenic granuloma, cherry angioma.
Self-limiting, usually within 1-2 months. Uncommonly, prolonged morbidity with persistent high fever, suppurative lymphadenitis, severe systemic symptoms. May be confused with lymphoma. Uncommonly, cat-scratch encephalopathy occurs. Antibiotic therapy has not been very effective in altering the course of the infection.
In the immunocompromised, azithromycin; in immunocompetent, spontaneous resolution occurs.
Clinical findings confirmed by demonstration of Bartonella bacilli on silver stain of lesional biopsy specimen or culture or antibody studies.
Course and Treatment
Rarely seen in persons with HIV disease successfully treated with ART. Untreated systemic infection causes significant morbidity and mortality. With effective antimicrobial therapy (erythromycin, doxycycline), lesions resolve within 1-2 weeks. As with other infections occurring in HIV disease, relapse may occur and require lifelong secondary prophylaxis.
Tularemia ICD-9: 021 ICD-10: A21
Etiology: Francisella tularensis, types A and B. After inoculation into skin, mucous membrane, lung (inhalation), or GI tract, F. tularensis reproduces and spreads through lymphatic channels to lymph nodes and bloodstream.
Transmission. Bite of insect vector (ticks, deer flies, body lice, other arthropods). Handling flesh of infected animals; inoculation of conjunctiva; ingestion of infected food; inhalation. Most US cases occur in June-September when arthropod transmission is most common.
Animal Reservoir. Rabbits, hares, muskrats, prairie dogs, foxes, squirrels, skunks, voles, beavers.
Incidence. Rare; <200 cases reported in the United States per year; underdiagnosed, underreported.
About 48 h after inoculation, pruritic papule develops at the site of trauma or insect bite followed by enlargement of regional lymph nodes. Fever to 41°C.
Inoculation site: Erythematous tender papule evolving to a vesicopustule, enlarging to crusted ulcer with raised, sharply demarcated margins (96 h) (Fig. 25-61). Depressed center that is often covered by a black eschar (chancriform). Primary lesion on finger/hand at the site of trauma or insect bite; groin or axilla after tick bite.
Other Cutaneous Findings. Exanthem may occur after bacteremia on trunk and extremities with macules, papules, petechiae. Erythema multiforme. Erythema nodosum.
Figure 25-61. Tularemia: primary lesion and regional adenopathy A crusted ulcer at the site of inoculation is seen on the dorsum of the left ring finger with associated axillary lymph node enlargement (chancriform syndrome). The infection occurred after the patient killed and skinned a rabbit.
Conjunctivae. In oculoglandular tularemia, F. tularensis is inoculated into conjunctiva, causing a purulent conjunctivitis with pain, edema, and congestion. Small yellow nodules occur on conjunctivae and ulcerate.
Regional Lymph Nodes. As the ulcer develops, nodes enlarge and become tender, i.e., chancriform syndrome (Fig. 25-58). If untreated, become suppurating buboes.
Acute cutaneous ulcer: Furuncle, paronychia, anthrax, P. multocida infection, sporotrichosis, M. marinum infection. Chancriform syndrome: Herpes simplex virus lymphadenitis, plague, cat-scratch disease.
Clinical diagnosis in a patient with chancriform syndrome with appropriate animal or insect exposure.
Untreated, mortality rate for ulceroglandular form is 5%; 1% if therapy initiated promptly.
Gentamycin, streptomycin, doxycycline, ciprofloxacin.
Cutaneous Pseudomonas Aeruginosa Infections
P. aeruginosa: Nonfastidious, motile; produce pyocyanin and pyoverdin, pigments that cause yellow to dark green to bluish color.
Ecology. Widespread in nature, inhabiting water, soil, plants, and animals, preferring moist environments. In healthy individuals, carriage rate of skin is low; pseudomonas are minimally invasive.
Transmission. Most invasive infections are hospital acquired. Entry sites wounds, ulcers, thermal burns; foreign bodies (IV or urinary catheter), aspiration/aerosolization into respiratory tract.
Green nails: P. aeruginosa grows as a biofilm on ventral or dorsal surface of abnormal nails. Onycholytic nails, e.g., psoriasis, onychomycosis, create a moist environment for Pseudomonas to colonize (Fig. 32-4). Less commonly, Pseudomonas can colonize the dorsal surface of fingernails associated with chronic paronychia. The onycholytic nail plate can be trimmed to eliminate the abnormal space.
Intertrigo: Gram-negative webspace intertrigo presents as macerated and eroded skin on interdigital toes. Pseudomonas is the most common cause. Usually occurs in the setting of hyperhidrosis and hydration of stratum corneum. Interdigital tinea pedis and erythrasma may also be present. Superficial intertrigo can progress with interdigital ulceration and soft-tissue infection.
External Otitis. Swimmer’s ear: Moist environment of external auditory canal provides medium for superficial infection, presenting as pruritus, pain, discharge; usually self-limited. Malignant external otitis occurs in elderly diabetic patients most commonly; may progress to deeper invasive infection.
Hot tub folliculitis: P. aeruginosa can infect multiple hair follicles during exposure in hot tubs or physiotherapy pools, presenting as multiple follicular pustules on the trunk (Fig. 31-28). Infection is self-limited.
Colonization of wounds: Thermal burns, stasis ulcers, pressure ulcers, surgical wounds more commonly colonized with Pseudomonas (Fig. 25-36) after prior treatment of S. aureus with systemic antibiotics, diabetes, and other host defense defects. Soft-tissue infection can occur in colonized wounds.
Soft-tissue infection and E. gangrenosum: Superficial infection can progress to cellulitis. E. gangrenosum is a necrotizing soft-tissue infection associated with blood vessel invasion, septic vasculitis, vascular occlusion, and necrosis (Fig. 25-29).
Pseudomonal bacteremia: Hematogenous dissemination of P. aeruginosa can seed the dermis, resulting in multiple tender subcutaneous nodules.
Clinical suspicion confirmed by culture of skin lesion.
Antibiotic according sensitivity of microbes. Surgical debridement.
Mycobacteria are rod-shaped or coccobacilli acid-fast bacilli (AFB); acid-fastness associated with composition of their cell walls. More than 120 species identified. Relatively few associated with human disease:
Hansen disease (Leprosy).
Buruli or Baimsdale ulcer disease is the third most common mycobacterial disease globally.
Hansen Disease (Leprosy) ICD-9: 030 ICD-10: A30
Etiology. Mycobacterium leprae.
Chronic granulomatous disease principally acquired during childhood/young adulthood.
Sites of infection. skin, peripheral nervous system, upper respiratory tract, eyes, testes.
Clinical manifestations, natural history, and prognosis of leprosy are related to the host response: Various types of leprosy (tuberculoid, lepromatous, etc.) represent the spectra of the host’s immunologic response (cell-mediated immunity).
Based on clinical, immunologic, and bacteriologic findings.
• Tuberculoid (TL): Localized skin involvement and/or peripheral nerve involvement; few organisms.
• Lepromatous (LL): Generalized involvement including skin, upper respiratory mucous membrane, reticuloendothelial system, adrenal glands, testes; many bacilli.
• Borderline (or “dimorphic”) (BL): Has features of both TL and LL. Usually many bacilli present, varied skin lesions: macules, plaques; progresses to TL or regresses to LL.
• Indeterminate forms.
• Transitional forms: See “Pathogenesis,” below.
Etiology and Epidemiology
Mycobacterium leprae: Obligate intracellular acid-fast bacillus; reproduces optimally at 27-30°C. Organism cannot be cultured in vitro. Infects skin and cutaneous nerves (Schwann cell basal lamina). In untreated patients, only 1% of organisms are viable. Grows best in cooler tissues (skin, peripheral nerves, anterior chamber of eye, upper respiratory tract, testes), sparing warmer areas of the skin (axilla, groin, scalp, and mid-line of back). Humans are main reservoirs of M. leprae. Wild armadillos (Louisiana) as well as mangabey monkeys and chimpanzees are naturally infected with M. leprae; armadillos can develop lepromatous lesions.
Incidence rate peaks at 10-20 years; prevalence peaks at 30-50 years. More common in males than in females. Inverse relationship between skin color and severity of disease; in black African, susceptibility is high, but there is predominance of milder forms of the disease, i.e., TL vis-à-vis LL.
Transmission. Uncertain. Likely spread from person to person in respiratory droplets.
Demography. Disease of developing world. In 2002, 763,000 new cases detected worldwide; 96 in the United States. Brazil, Madagascar, Mozambique, Tanzania, and Nepal had 90% of cases. Risk groups: Close contacts with patients with untreated, active, predominantly multibacillary disease, and persons living in countries with highly endemic disease. Most individuals have natural immunity and do not develop disease.
Pathogenesis. Clinical spectrum of leprosy depends exclusively on variable limitations in host’s capability to develop effective cellmediated immunity to M. leprae. Organism is capable of invading and multiplying in peripheral nerves and infecting and surviving in endothelial and phagocytic cells in many organs. Subclinical infection with leprosy is common among residents in endemic areas. Clinical expression of leprosy is development of a granuloma; patient may develop a “reactional state,” which may occur in some form in >50% of certain groups of patients.
Granulomatous Spectrum of Leprosy
• High-resistance tuberculoid response (TT).
• Low- or absent-resistance lepromatous pole (LL).
• Morphic or borderline region (BB).
• Two intermediary regions.
• Borderline lepromatous (BL).
• Borderline tuberculoid (BT).
In order of decreasing resistance, the spectrum is TT, BT, BB, BL, LL.
Immunologic Responses. Immune responses to M. leprae can produce several types of reactions associated with a sudden change in the clinical status.
Lepra Type 1 Reactions. Acute or insidious tenderness and pain along affected nerve(s), associated with loss of function.
Lepra Type 2 Reactions. Erythema nodosum leprosum (ENL). Seen in half of LL patients, usually occurring after initiation of antilepromatous therapy, generally within the first 2 years of treatment. Massive inflammation with erythema nodosum-like lesions.
Lucio Reaction. Individuals with diffuse LL develop shallow, large polygonal sloughing ulcerations on the legs. The reaction appears to be either a variant of ENL or secondary to arteriolar occlusion.
Incubation period is 2-40 years (most commonly 5-7 years). Onset is insidious and painless; first affects peripheral nervous system with persistent or recurrent painful paresthesias and numbness without any visible clinical signs. At this stage, there may be transient macular skin eruptions; blister, but lack of awareness of trauma. Neural involvement leads to muscle weakness, muscle atrophy, severe neuritic pain, and contractures of the hands and feet.
Tuberculoid Leprosy (TT, BT). Few well-defined hypopigmented hypesthetic macules (Fig. 25-62) with raised edges and varying in size from a few millimeters to very large lesions covering the entire trunk. Erythematous or purple border and hypopigmented center. Sharply defined, raised; often annular; enlarge peripherally. Central area becomes atrophic or depressed. Advanced lesions are anesthetic, devoid of skin appendages (sweat glands, hair follicles). Any site including the face. TT: Lesions may resolve spontaneously; not associated with lepra reactions. BT: Does not heal spontaneously; type 1 lepra reactions may occur.
Figure 25-62. Leprosy: tuberculoid type Well-defined, hypopigmented, slightly scaling, anesthetic macules and plaques on the posterior trunk.
Nerve Involvement: May be a thickened nerve on the edge of the lesion; large peripheral nerve enlargement frequent (ulnar, posterior auricular, peroneal, posterior tibial nerves). Skin involvement is absent in neural leprosy. Nerve involvement associated with hypesthesia (pinprick, temperature, vibration) and myopathy.
Borderline BB Leprosy. Lesions are intermediate between tuberculoid and lepromatous and are composed of macules, papules, and plaques (Fig. 25-63). Anesthesia and decreased sweating are prominent in the lesions.
Figure 25-63. Leprosy: borderline-type A 26-year-old Vietnamese male. (A) Well-demarcated, infiltrated, erythematous plaques on the face. (B) Identical red plaques on the lower back.
Lepromatous Leprosy (LL, BL). Skin-colored or slightly erythematous papules/nodules. Lesions enlarge; new lesions occur and coalesce. Later: symmetrically distributed nodules, raised plaques, diffuse dermal infiltrate, which on face results in loss of hair (lateral eyebrows and eyelashes) and leonine facies (lion’s face; Fig. 25-64). Diffuse lepromatosis, occurring in western Mexico, Caribbean, presents as diffuse dermal infiltration and thickened dermis. Bilaterally symmetric involving earlobes, face, arms, and buttocks, or less frequently the trunk and lower extremities. Tongue: nodules, plaques, or fissures.
Figure 25-64. Diffuse skin infiltration, multiple nodular lesions, and sensory loss are the key hallmarks of lepromatous leprosy (LL). This patient presented lesions on the upper part of the thorax, forehead, ears, nose, lips, perilabial, and mentonian regions, as well as lax skin of the malar and palpebral superior regions, with muscle force impairment on the left side. Superciliary and ciliary madarosis were also present. Ulnar and tibial posterior nerves were enlarged. A Ziehl-Neelsen stained skin smear had a 6+ bacterial index for acid-fast bacilli in clumps, and ELISA titration for anti-PGL-1 IgM was 3.445 (cutoff 0.295). The 12-month World Health Organization multidrug therapy regimen and prednisone were prescribed, with significant improvement. LL is the anergic form of leprosy; it generates an exacerbated but inefficient humoral immune response, leading to highly infectious patients. Mycosis fungoides, neurofibromatosis, sarcoidosis, amyloidosis, syphilis, anergic leishmaniasis, and lobomycosis are among diseases in the differential diagnosis. (Courtesy of C. G. Salgado and J. G. Barreto, Pará Federal University, Brazil.)
Nerve Involvement: More extensive than in TT.
Other Involvement: Upper respiratory tract, anterior chamber of eye, testes.
Immunologically mediated inflammatorystates, occurring spontaneously or after initiation of therapy.
Lepra Type 1 Reactions: Skin lesions become acutely inflamed, associated with edema and pain; may ulcerate. Edema most severe on face, hands, and feet.
Lepra Type 2 Reactions (ENL): Present as painful red skin nodules arising superficially and deeply, in contrast to true erythema nodosum. Lesions form abscesses or ulcerate; occur most commonly on face and extensor limbs.
Lucio Reaction: Occurs only in patients from Mexico or Caribbean with diffuse LL. Presents as irregularly shaped erythematous plaques; lesions may resolve spontaneously or undergo necrosis with ulceration.
Extremities: Sensory neuropathy, plantar ulcers, secondary infection; ulnar and peroneal palsies (Fig. 25-65), Charcot joints. Squamous cell carcinoma can arise in chronic foot ulcers (Fig. 11-13).
Figure 25-65. Leprosy: lepromatous type A 60-year-old Vietnamese female with treated advanced disease. Ulnar palsy, loss of digits on right hand, and saddle-nose deformity associated with loss of nasal cartilage are seen.
Nose: Chronic nasal congestion, epistaxis; destruction of cartilage with saddle-nose deformity (Fig. 25-63).
Eyes: Cranial nerve palsies, lagophthalmus, corneal insensitivity. In LL, anterior chamber can be invaded with uveitis, glaucoma, cataract formation. Corneal damage can occur secondary to trichiasis and sensory neuropathy, secondary infection, and muscle paralysis.
Testes: May be involved in LL with resultant hypogonadism.
Complications of Leprosy: Squamous cell carcinoma can arise in chronic neurotrophic ulcers on the lower extremities (see Fig. 11-13). The tumors are usually low-grade malignancies but can metastasize to regional lymph nodes and cause death. Secondary amyloidosis with hepatic and renal abnormalities.
Hypopigmented lesions with granulomas.
Sarcoidosis, leishmaniasis, NTM infection, lymphoma, syphilis, granuloma annulare.
Slit-Skin Smears. A small skin incision is made; the site is then scraped to obtain tissue fluid from which a smear is made and examined after Ziehl-Neelsen staining. Specimens are usually obtained from both earlobes and two other active lesions. Negative BIs are seen in paucibacillary cases, treated cases, and cases examined by an inexperienced technician.
Culture. M. leprae has not been cultured in vitro; however, it does grow when inoculated into the mouse foot pad. Routine bacterial cultures to rule out secondary infection.
PCR. M. leprae DNA detected by this technique makes the diagnosis of early paucibacillary leprosy and identifies M. leprae after therapy.
Serology. Measure IgM antibodies to phenolic glycolipid-1 (PGL-1).
Dermatopathology. TL shows epithelioid cell granulomas forming around dermal nerves; AFB are sparse or absent. LL shows an extensive cellular infiltrate separated from the epidermis by a narrow zone of normal collagen. Skin appendages are destroyed. Macrophages are filled with M. leprae, having abundant foamy or vacuolated cytoplasm (lepra cells or Virchow cells).
Made if one or more of the cardinal findings are detected: patient from endemic area, skin lesions characteristic of leprosy with diminished or loss of sensation, enlarged peripheral nerves, finding of M. leprae in skin or, less commonly, other sites.
After the first few years of drug therapy, the most difficult problem is management of the changes secondary to neurologic deficits—contractures and trophic changes in the hands and feet. Uncommonly, secondary amyloidosis with renal failure can complicate long-standing leprosy. Lepra type 1 reactions last 2-4 months in individuals with BT and up to 9 months in those with BL. Lepra type 2 reactions (ENL) occur in 50% of individuals with LL and 25% of those with BL within the first 2 years of treatment. ENL may be complicated by uveitis, dactylitis, arthritis, neuritis, lymphadenitis, myositis, orchitis. Lucio reaction or phenomenon occurs secondary to vasculitis with subsequent infarction.
General principles of treatment:
• Tuberculoid: dapsone plus rifampin.
• Lepromatous: dapsone plus clofazimine plus rifampin.
• Eradicate infection with antilepromatous therapy.
• Prevent and treat reactions (prednisone, thalidomide).
• Reduce the risk of nerve damage.
• Educate patient to deal with neuropathy and anesthesia.
• Treat complications of nerve damage.
• Rehabilitate patient into society.
Management involves a broad multidisciplinary approach including orthopedic surgery, podiatry, ophthalmology, and physical therapy.
Cutaneous Tuberculosis ICD-9: 017.0 ICD-10: A18.4
Etiology. Mycobacterium tuberculosis complex. Commonly infects lungs; rarely skin.
Transmission. Airborne spread of droplet nuclei from those with infectious pulmonary Tb to lungs. Historically, traumatic inoculation into skin and ingestion of M. bovis contaminated milk.
Cutaneous Infection. Exogenous inoculation into skin. Direct extension from deeper tissues such as joint; lymphatic spread to skin; hematogenous spread to skin.
Exogenous Inoculation to Skin. Primary inoculation tuberculosis (PIT), i.e., tuberculous chancre: occurs at inoculated site in nonimmune host. Tuberculosis verrucosa cutis (TVC): occurs at inoculated site in individual with prior tuberculosis infection.
Tuberculosis due to bacille Calmette-Guérin (BCG) immunization.
Endogenous Spread to Skin. Lymphatics, hematogenous, bodily fluids (sputum, feces, urine). Lupus vulgaris. Scrofuloderma. Metastatic tuberculosis abscess. Acute miliary tuberculosis. Orificial tuberculosis.
Type of clinical lesion depends on route of cutaneous inoculation and immunologic status of the host.
• Cutaneous inoculation results in a tuberculous chancre in the nonimmune host and TVC in the immune host.
• Direct extension from underlying tuberculous infection, i.e., lymphadenitis or tuberculosis of bones and joints, results in scrofuloderma.
• Lymphatic spread to skin results in lupus vulgaris.
• Hematogenous dissemination results in acute miliary tuberculosis, lupus vulgaris, or metastatic tuberculosis abscess.
• Autoinoculation from body fluids such as sputum, urine, feces results in orificial tuberculosis.
Globally, the incidence of cutaneous tuberculosis is increasing, associated with HIV disease. Problem of multidrug resistance (MDR) is also common in persons with HIV disease.
PIT. Initially, papule occurs at the inoculation site 2-4 weeks after inoculation. Lesion enlarges to a painless ulcer, tuberculous chancre (Fig. 25-66) with shallow granular base. Older ulcers become indurated with thick crusts. Deeper inoculation results in subcutaneous abscess. Most common on exposed skin at sites of minor injuries. Oral ulcers on gingiva or palate occur after ingestion of bovine bacilli in nonpasteurized milk. Regional lymphadenopathy occurs several weeks after appearance of ulcer (chancriform syndrome).
Figure 25-66. Primary inoculation tuberculosis A large, ulcerated nodule at the site of Mycobacterium tuberculosis inoculation on the right thigh associated with inguinal lymphadenopathy. The erythematous papules on the left forearm occurred at the site of tuberculin testing.
TVC. Initial papule with violaceous halo. Evolves to hyperkeratotic, warty, firm plaque (Fig. 25-67). Clefts and fissures occur from which pus and keratinous material can be expressed. Border often irregular. Lesions are usually single, but multiple lesions occur. Most commonly on dorsolateral hands and fingers. In children, lower extremities, knees. No lymphadenopathy.
Figure 25-67. Tuberculosis verrucosa cutis A 40-yearold male with warty and crusted plaques on the dorsum of the R-hand for 6 months. [From Sethi A. Tuberculosis and infections with atypical Mycobacteria. In Goldsmith LA et al. (eds.). Fitzpatrick’s Dermatology in General Medicine, 8th ed. New York, McGraw-Hill, 2012.]
Lupus Vulgaris. Initial papule ill defined and soft and evolves into well-defined, irregular plaque (Fig. 25-68). Reddish-brown. Diascopy (glass slide pressed against skin) shows semitranslucent “apple jelly” color (i.e., orange-tan). Lesions are characteristically soft and friable. Surface is initially smooth or slightly scaly but may become hyperkeratotic. Hypertrophic forms result in soft tumorous nodules. Ulcerative forms present as punched-out, often serpiginous ulcers surrounded by soft, brownish infiltrate. Usually solitary, but several sites may occur. Most lesions on the head and neck, most often on nose, ears, or scalp. Lesions on ears or nose can result in destruction of underlying cartilage. Scarring is prominent. Characteristically new brownish infiltrates occur within atrophic scars.
Figure 25-68. Lupus vulgaris Reddish-brown plaque, which on diascopy exhibits the diagnostic yellow-brown apple-jelly color. Note nodular infiltration of the earlobe, scaling of the helix, and atrophic scarring in the center of the plaque.
Scrofuloderma. Firm subcutaneous nodule that initially is freely movable; lesion then becomes doughy and evolves into irregular, deep-seated node or plaque that liquefies and perforates (Fig. 25-69). Ulcers and irregular sinuses, usually of linear or serpiginous shape, discharge pus or caseous material. Edges are undermined, inverted, with dissecting subcutaneous pockets alternating with soft, fluctuating infiltrates and bridging scars. Most often occurs in the parotid, submandibular, and supraclavicular regions; lateral neck; scrofuloderma most often results from contiguous spread from affected lymph nodes or tuberculous bones (phalanges, sternum, ribs) or joints.
Figure 25-69. Scrofuloderma: lateral chest wall. Two ulcers on the chest wall and axilla are associated with underlying sinus tracts.
Metastatic Tuberculosis Abscess. Subcutaneous abscess, nontender, “cold,” fluctuant. Coalescing with overlying skin, breaking down and forming fistulas and ulcers (Fig. 25-70). Single or multiple lesions, often at sites of previous trauma.
Figure 25-70. Metastatic tuberculous abscess on the scalp An infant with combined immunodeficiency. Note abscess formation and discharge of purulent material but little inflammation.
Acute Miliary Tuberculosis. Exanthem. Disseminated lesions are minute macules and papules or purpuric lesions. Sometimes vesicular and crusted. Removal of crust reveals umbilication. Disseminated on all parts of body, particularly trunk.
Orificial Tuberculosis. Small yellowish nodule on mucosa breaks down to form painful circular or irregular ulcer (Fig. 25-71) with undermined borders. Surrounding mucosa swollen, edematous, and inflamed. Since orifical tuberculosis results from autoinoculation of mycobacteria from progressive tuberculosis of internal organs, it is usually found on the oral, pharyngeal (pulmonary tuberculosis), vulvar (genitourinary tuberculosis), and anal (intestinal tuberculosis) mucous membranes. Lesions may be single or multiple, and in the mouth most often occur on the tongue, soft and hard palate, or lips.
Figure 25-71. Orificial tuberculosis: lips A large, very painful ulcer on the lips of this patient with advanced cavitary pulmonary tuberculosis.
Clinical findings, tuberculin skin testing (Fig. 25-72), dermatopathology, confirmed by isolation of M. tuberculosis on culture or by PCR.
Figure 25-72. Purified protein derivative or Mantoux test: positive test A 31-year-old Taiwanese female with psoriasis, with a negative skin test 1 year previously, was retested prior to beginning etanercept. She had become infected while visiting her father, who had pulmonary tuberculosis, in Taiwan. A red plaque with surrounding erythema is seen at the test site.
The course of cutaneous tuberculosis is quite variable, depending on the type of cutaneous infection, amount of inoculum, extent of extracutaneous infection, age of the patient, immune status, and therapy.
Only PIT and TVC are limited to the skin. All other patterns of cutaneous tuberculosis are associated with systemic infection that has disseminated secondarily to skin. As such, therapy should be aimed at achieving a cure, avoiding relapse, and preventing emergence of drug-resistant mutants.
Antituberculous Therapy. Prolonged antituberculous therapy with at least two drugs is indicated for all cases of CTb except for TVC that can be excised.
• Standard antituberculous therapy:
• Isoniazid (5 mg/kg daily) plus
• Rifampin (600 mg/kg daily)
• Supplemented in initial phases with:
• Ethambutol (25 mg/kg daily) and/or
• Streptomycin (10-15 mg/kg daily) and/or
• Pyrazinamide (15-30 mg/kg daily)
Isoniazid and rifampin for at least 9 months; can be shortened to 6 months if four drugs are given during the first 2 months.
Multidrug Resistant (MDR) Tb. Incidence is increasing.
Nontuberculous Mycobacterial Infections
ICD-9: 031.1 ICD-10: A31.1
Nontuberculous mycobacteria (NTM) defined as mycobacteria other than M. tuberculosis complex and M. leprae. Occur naturally in the environment: M. marinum, M. ulcerans, M. fortuitum complex, M. abscessus, M. avium-intracellulare, M. haemophilum.
Infection. Capable of causing primary infections in otherwise healthy individuals and more serious infection with host defense defects, e.g.,
Immunocompetent individuals: primary cutaneous infections at sites of inoculation. Nodules, lymphocutaneous lesions, or nodular lymphangitis.
Immunocompromised host: disseminated mucosal and cutaneous lesions.
Diagnosis. Detection of mycobacteria histochemically or by culture on specific media. New molecular techniques based on DNA amplification accelerate diagnosis, identify common sources of infection, reveal new types of NTM.
Treatment. Clarithromycin, rifampicin, fluoroquinolones, minocycline.
Mycobacterium Marinum Infection
Etiology. M. marinum, an environmental nontuberculous mycobacterium. Infection usually follows traumatic inoculation in aqueous environment, i.e., fish tank, pool, water. Recent case reports of M. marinum infection with antitumor necrosis factor therapy.
Demography. Healthy adults. More invasive or disseminated infections with host defense defects.
Incubation Period. Variable: usually weeks to months after inoculation. Lesions may be asymptomatic or tender.
Inoculation Site. Papule(s) enlarging to inflammatory (Fig. 25-73), red to red-brown nodule or plaque 1-4 cm in size on dominant hand. Surface of lesions may be hyperkeratotic or verrucous (Fig. 25-74). May become ulceratedwith superficial crust, granulation tissue base, ± serosanguineous, or purulent discharge. In some cases, small satellite papules and draining sinuses may develop. Usually solitary, over bony prominence. More extensive soft-tissue infection may occur with host defense defects. Atrophic scarring follows spontaneous regression or successful therapy.
Figure 25-73. M. marinum: inoculation site infection on the foot A 31-year-old male with painful indurated plaque on the lateral dorsal foot. The lesion arose at the site of a small blister 1 year ago while in Afghanistan. Three previous biopsies and tissue cultures had been unsuccessful at making a diagnosis. After intralesional injection of triamcinolone 1.5 mg/mL, acid-fast bacilli were identified in the biopsy specimen and M. marinum isolated on culture. He was successfully treated with four antimycobacterial agents.
Figure 25-74. M. marinum infection: verrucous plaque A red-violet, verrucous plaque on the dorsum of the right thumb of a fist-tank hobbist at the site of an abrasion.
Nodular Lymphangitis. Deep-seated nodules in a linear configuration on hand and forearm exhibit lymphocutaneous spread (Fig. 25-75). Boggy inflammatory reaction may mimic bursitis, synovitis, or arthritis about the elbow, wrist, or interphalangeal joints. Tenosynovitis, septic arthritis, osteomyelitis. Host defense defects.
Figure 25-75. M. marinum: soft-tissue infection and lymphangitis beginning on finger A 48-year-old female with painful swelling of the right middle finger for 4 months. She recalled cleaning a fish tank several weeks before the distal digital became red and tender. The finger and hand became progressively more inflamed and red nodules appeared on the forearm. Slight enlargement of axillary nodes was detected.
Disseminated Infection. Rare. May occur host defense defects.
Regional lymphadenopathy uncommon.
History of trauma in an aqueous environment, clinical findings, confirmed by isolation of M. marinum on culture. M. marinum grows at 32°C (but not at 37°C) in 2-4 weeks. Early lesions yield numerous colonies. Lesions 3 months or older generally yield few colonies.
Lesional biopsy. Acid-fast stain demonstrates M. marinum only in approximately 50% of cases.
Usually self-limited but can remain active for a prolonged period. Single papulonodular lesions resolve spontaneously within 3 months to 3 years; nodular lymphangitis can persist for years. With host defense defects, more extensive deep infection can occur.
Drug of first choice: clarithromycin and either rifampin or ethambutol for 1-2 months after lesions have resolved (3-4 months). Minocycline alone may be effective.
Mycobacterium Ulcerans Infection
ICD-9: 031.1 ICD-10: A31.1
Synonyms: Buruli ulcer or Buruli ulcer disease in Africa. Bairnsdale or Daintree ulcer in Australia.
Etiology. M. ulcerans. An environmental habitat for the organism has not been established. Incidence: third most common mycobacterial infection after tuberculosis and leprosy.
Transmission. Inoculation probably via minor trauma occurring in wet, marshy, or swampy sites. Bites of aquatic insects; M. ulcerans replicates in insect salivary glands; in endemic areas, 5-10% of aquatic insects have microbe in salivary gland.
Demography. Occurs in >30 countries. Tropical regions of West Africa; Australia, Papua New Guinea; Central Mexico.
Pathogenesis. M. ulcerans produces polypeptide toxin (mycolactone), which suppresses immune response to microbe.
Incubation period approximately 3 months. The early nodule at the site of trauma and subsequent ulceration are usually painless. Fever, constitutional findings are usually absent.
Painless subcutaneous swelling occurs at the site of inoculation. Papule(s), nodule(s), and plaques are often overlooked. Lesion enlarges and ulcerates. The ulcer extends into the subcutaneous fat, and its margin is deeply undermined (Fig. 25-76). Ulcerations may enlarge to involve an entire extremity. Legs more commonly involved, sites of trauma. Any site may be involved. Soft tissue and bony involvement can occur. As ulcerations healed, scarring and disabling deformities may occur. Osteomyelitis may occur.
Figure 25-76. M. ulcerans: Buruli ulcer A 15-year-old Ugandan male with a huge ulcer with a clean base and undermined margins extends into the subcutaneous tissue. (Courtesy of M. Dittrich, MD.)
Identification of microbe on culture or by PCR.
Dermatopathology. Necrosis originates in interlobular septa of subcutis. Poor inflammatory response despite clusters of extracellular bacilli. Granulation with giant cells but no caseation necrosis. AFB are always demonstrable.
Sporotrichosis, nocardiosis, phaeohyphomycosis, squamous cell carcinoma.
Mycobacterium Fortuitum Complex Infections
ICD-9: 031.1 ICD-10: A31.1
Etiology. M. fortuitum, M. chelonae, M. abscessus. Organisms are widely distributed in soil, dust, and water.
Natural Reservoirs. Nosocomial environments: municipal water supplies, moist areas in hospitals, contaminated biological agents.
Cutaneous infections account for 60% of infections.
Transmission. Inoculation via traumatic puncture wounds, percutaneous catheterizations or injections. Whirlpool footbaths in nail salons (M. fortuitum).
Because of delay in diagnosis and treatment, lesions are often extensive. Ulcerations persist for months to years. Spontaneous healing occurs eventually in some patients; scarring, contracture of the limb, and lymphedema. Malnutrition and anemia delay healing.
Antimycobacterial Drug Therapy. Rifampicin and streptomycin combined with surgery. Combination of rifampicin and ciprofloxacin may be effective.
Surgery. Excision followed by grafting.
Incubation period usually within 1 month (range 1 week to 2 years).
Skin and Soft-Tissue Infections. Nodular on lower legs following foot baths at nail salons, so called furunculosis (Fig. 25-77); shaving legs provides a portal of entry. Wound infections at surgical sites or sites of trauma. Multiple nodules, abscesses, and crusted ulcers with host defense defects (Figs. 25-78 and 25-79).
Figure 25-77. M. fortuitum infection A 45-year-old female with erythematous tender nodules on the lower legs. The lesions occurred several weeks after a pedicure in a foot care salon. Shaving of legs may have facilitated the infection. M. fortuitum was isolated on culture of lesional biopsy specimen.
Figure 25-78. Multiple sites of soft-tissue infection lower leg: Mycobacterium chelonae A 74-year-old female with chronic progressive lung disease treated with prednisone and azathioprine developed soft-tissue infections with multiple abscesses on hands, lower legs, and feet. M. chelonae was isolated on culture of biopsy specimen.
Figure 25-79. M. chelonae abscess on L-dorsolateral foot A 74-year-old female treated with prednisone and azathioprine. M. chelonae isolated on lesional biopsy specimen.
Lesional skin biopsy specimen or identify by PCR.
Dermatopathology. Necrosis is often present without caseation; AFB can be seen within microabscesses.
The infection becomes chronic unless treated with antimycobacterial therapy, ± surgical debridement.
Antimycobacterial chemotherapy. Surgical debridement with delayed closure for localized infections.
Lyme Disease ICD-9: 088.81 ICD-10: A69.2
Etiologic agent: Borrelia spirochetes. Transmitted to humans by the bite of an infected blacklegged or ixodid tick.
Stage 1 early localized disease: Up to 30 days post tick bite. Erythematous plaque at the tick bite site, erythema migrans, noted in 70-80% of cases. Acute illness syndrome (fever, chills, myalgia, headache, weakness, photophobia). Lymphocytoma.
Stage 2 early disseminated disease: Days to weeks post tick bite. Secondary lesions. Meningitis, cranial neuritis (8%), radiculoneuritis (4%), peripheral neuritis. Carditis: AV nodal block (1%). Migratory musculoskeletal pain (33%), arthralgias.
Stage 3 late disseminated disease: Persistent infection, developing months or years later: intermittent or persistent arthritis, chronic encephalopathy or polyneuropathy, acrodermatitis.
Posttreatment Lyme disease syndrome: 10-20% of treated patients have persistent symptoms.
Etiology and Epidemiology
Etiologic Agent. Borrelia burgdorferi. Clinical variations of disease may be related to differences in the various causative strains.
Vector. Infected nymphal tick of genus Ixodes ricinus complex. Three stages of tick development: larva, nymph, adult; each stage requires blood meal. The tiny nymphal tick transmits B. burgdorferi to humans in early summer. Preferred host of adult I. scapularis is white-tailed deer, which is not involved in the life cycle of spirochete but is critical to the survival of the tick.
Season. In the Midwestern and eastern United States, late May through early autumn (80% of early LD begins in June and July). In the Pacific Northwest, January through May.
Risk for Exposure. Strongly associated with prevalence of tick vectors and proportion of those ticks that carry B. burgdorferi. In the northeastern United States with endemic disease, the infection rate of the nymphal I. scapularistick with B. burgdorferi is commonly 20-35%.
Incidence. LD is the most common vectorborne infection in the United States, with 30,000 cases reported (2010). Cases reported in all 50 states except Hawaii.
Pathogenesis. After inoculation into the skin, spirochetes replicate and migrate centrifugally, producing the EM lesion, and invade vessels, spreading hematogenously to other organs. The spirochete has a particular trophism for tissues of the skin, nervous system, and joints. The organism persists in affected tissues during all stages of the illness. The immune response to the spirochete develops gradually. Specific IgM antibodies peak between the third and sixth weeks after disease onset. The specific IgG response develops gradually over months. Proinflammatory cytokines, TNF-α, and IL-1 are produced in affected tissues.
Incubation period for EM: 3-32 days after tick bite. Cardiac manifestations 35 days (3 weeks to >5 months after tick bite). Neurologic manifestations: average 38 days (2 weeks to months) after tick bite. Rheumatologic manifestations: 4 days to 2 years after bite.
Prodrome. With disseminated infection (stage 2), malaise, fatigue, lethargy, headache, fever, chills, stiff neck, arthralgia, myalgia, backache, anorexia, sore throat, nausea, dysesthesia, vomiting, abdominal pain, photophobia.
History. Because of the small size (poppy seed) of nymphal tick, most patients are unaware of tick bite; adults are sesame seed size. Ixodid tick bites are asymptomatic. Removal of the nymphal tick within 18 h of attachment may preclude transmission. EM may be associated with burning sensation, itching, or pain. Only 75% of patients with Lyme disease exhibit EM. Joint complaints more common in North America. Neurologic involvement more common in Europe. With persistent disease, chronic fatigue.
Stage 1 Localized Infection. EM. Initial erythematous macule or papule expanding centrifugally within days to form lesion with a distinct red border at the bite site (Fig. 25-80). Maximum median diameter is 15 em. As EM expands, site may remain uniformly erythematous, or several rings of varying shades of red with concentric rings (targetoid or bull’s eye lesions). When occurring on the scalp, only a linear streak may be evident on the face or neck (Fig. 25-81). Multiple EM lesions are seen with multiple bite sites. Most common sites: thigh, groin, axilla. Center may become indurated, vesicular, ecchymotic, or necrotic. As EM evolves, postinflammatory hyperpigmentation, transient alopecia, and desquamation may occur.
Figure 25-80. Lyme borreliosis: erythema migrans (EM) on upper thigh A 75-year-old male noted an asymptomatic red plaque on his thigh the day of the examination (A). He felt well, and was unaware of tick bite. Doxycycline, 100 mg BID, was given and he experienced flu-like symptoms (Jarisch-Herxheimer reaction). Four days after beginning treatment, the EM lesion is much larger (B); symptoms had resolved.
Figure 25-81. Lyme borreliosis: erythema migrans on face Serpiginous erythematous lesion on the forehead represents the margin of a large lesion occurring on the scalp.
Borrelial Lymphocytoma. Mainly seen in Europe. Usually arises at the site of tick bite. Some patients have a history of EM; others may show concomitant EM located around or near the lymphocytoma. Usually presents as a solitary bluish-red nodule (Fig. 25-82). Sites of predilection: earlobe (children), nipple/areola (adults), areola, scrotum; 3-5 cm in diameter.
Figure 25-82. Lyme borreliosis: lymphocytoma cutis Solitary, red-purple nodule on the characteristic site of the ear.
Other Cutaneous Findings. Malar rash, diffuse urticaria, subcutaneous nodules (panniculitis).
Stage 2 Disseminated Infection. Secondary Lesions. Secondary lesions resemble EM but are smaller, migrate less, and lack central induration and may be scaly. Lesions occur at any site except the palms and soles. A few or dozens of lesions may occur; can become confluent.
Stage 3 Persistent Infection. Acrodermatitis chronica atrophicans associated with B. afzelii infection in Europe and Asia. More common in elderly women. Initially, diffuse or localized violaceous erythema, usually on one extremity, accompanied by mild to prominent edema. Extends centrifugally over several months to years, leaving central areas of atrophy, veins and subcutaneous tissue become prominent (Fig. 25-83). Localized fibromas and plaques are seen as subcutaneous nodules around the knees and elbows.
Figure 25-83. Lyme borreliosis: acrodermatitis chronica atrophicans: end stage Advanced atrophy of the epidermis and dermis with associated violaceous erythema of legs and feet; the visibility of the superficial veins is striking.
Erythema Migrans. Insect bite (annular erythema caused by ticks, mosquitoes, Hymenoptera), epidermal dermatophytoses, allergic contact dermatitis, herald patch of pityriasis rosea, fixed drug eruption.
Lyme disease-like illness with exposure in Midwest and southern United States transmitted by Lone Star tick (Amblyomma americanum); referred to as southern tick-associated rash illness. Secondary Lesions. Secondary syphilis, pityriasis rosea, erythema multiforme, urticaria.
Skin Biopsy of EM. Deep and superficial perivascular and interstitial infiltrate containing lymphocytes and plasma cells with some degree of vascular damage (mild vasculitis or hypervascular occlusion). Spirochetes can be demonstrated in up to 40% of EM biopsy specimens.
CDC recommends a two-step approach: http://www.cdc.gov/lyme/diagnosistreatment/LabTest/TwoStep/
Diagnosis of early LB made on characteristic clinical findings in a person living in or having visited an endemic area; does not require laboratory confirmation. Diagnosis of late LB confirmed by specific serologic tests.
After adequate treatment, early lesions resolve within 2 weeks, and late manifestations are prevented. Late manifestations identified early usually clear after adequate antibiotic therapy; however, delay in diagnosis may result in permanent joint or neurologic disabilities. EM (short duration of infection) treated with antimicrobial agents does not confer protective immunity. If LB goes untreated for months, immunity may develop that protects against reinfection for years.
See Figure 25-84.
FIGURE 25-84 Algorithm for the treatment of the various acute or chronic manifestations of Lyme borreliosis Relapse may occur with any of these regimens, and a second course of treatment may be necessary. AV, atrioventricular. [AC Steere: Chap. 157 in Harrison’s Principles of Internal Medicine, 16ed, D Kasper et al (eds). New York, McGraw-Hill, 2005.