Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology, Seventh Edition

SECTION 20

Skin Signs of Hematologic Disease

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Thrombocytopenic Purpura

ICD-9: 287.31 image ICD-10: D69.3 image

image Thrombocytopenic purpura (TP) is characterized by cutaneous hemorrhages occurring in association with a reduced platelet count.

image Occur at sites of minor trauma/pressure (platelet count <40,000/μL) or spontaneously (platelet count <10,000/μL).

image Due to decreased platelet production, splenic sequestration, or increased platelet destruction.

image Decreased platelet production. Direct injury to bone marrow, drugs (cytosine arabinoside, daunorubicin, cyclophosphamide, busulfan, methotrexate, 6-mercaptopurine, vinca alkaloids, thiazide diuretics, ethanol, estrogens), replacement of bone marrow, aplastic anemia, vitamin deficiencies, Wiskott–Aldrich syndrome.

image Splenic sequestration. Splenomegaly, hypothermia.

image Increased platelet destruction. Immunologic: autoimmune TP, drug hypersensitivity (sulfonamides, quinine, quinidine, carbamazepine, digitoxin, methyldopa), after transfusion. Nonimmunologic: infection, prosthetic heart valves, disseminated intravascular coagulation, thrombotic TP.

image Skin Lesions. Petechiae—small (pinpoint to pinhead), red, nonblanching macules that are not palpable and turn brown as they get older (Fig. 20-1); later acquiring a yellowish-green tinge. Ecchymoses—black-and-blue spots; larger area of hemorrhage. Vibices—linear hemorrhages (Fig. 20-1), due to trauma or pressure. Most common on legs and upper trunk, but may be anywhere.

image Mucous Membranes. Petechiae—most often on palate (Fig. 20-2), gingival bleeding.

image General Examination. Possible CNS hemorrhage, anemia.

image Laboratory Hematology. Thrombocytopenia.

image Serology. Rule out HIV disease.

image Lesional Skin Biopsy (usually can be controlled by suturing biopsied site) to rule out vasculitis

image Differential diagnosis. Senile purpura, purpura of scurvy, progressive pigmentary purpura (Schamberg disease), purpura following severe Valsalva maneuver (coughing, vomiting/retching), traumatic purpura, factitial or iatrogenic purpura, vasculitis.

image Management. Identify underlying cause and correct, if possible. Oral glucocorticoids, high-dose IV immunoglobulins, platelet transfusion, chronic ITP: splenectomy may be indicated.

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Figure 20-1. Thrombocytopenic purpura Multiple petechiae on the upper arm of an HIV-infected 25-year-old male were the presenting manifestation of his disease. The linear arrangement of petechiae at the site of minor trauma is called vibices.

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Figure 20-2. Thrombocytopenic purpura Can first manifest on the oral mucosa or conjunctiva. Here, multiple petechial hemorrhages are seen on the palate.

Disseminated Intravascular Coagulation

ICD-9: 256.8 image ICD-10: D65 image

image Disseminated intravascular coagulation (DIC) is a widespread blood clotting disorder occurring within blood vessels.

image Associated with a wide range of clinical circumstances: bacterial sepsis, obstetric complications, disseminated malignancy, massive trauma.

image Manifested by purpura fulminans (cutaneous infarctions and/or acral gangrene) or bleeding from multiple sites.

image The spectrum of clinical symptoms associated with DIC ranges from relatively mild and subclinical to explosive and life threatening.

image Synonyms: Purpura fulminans, consumption coagulopathy, defibrination syndrome, coagulation fibrinolytic syndrome.

Epidemiology

Age of Onset. All ages; occurs in children.

Etiology and Pathogenesis

• Events that initiate DIC: Tumor products, crushing trauma, extensive surgery, severe intracranial damage; retained contraception products, placental abruption, amniotic fluid embolism; certain snake bites; hemolytic transfusion reaction; acute promyelocytic leukemia.

• Extensive destruction of endothelial surfaces: Vasculitis in Rocky Mountain spotted fever, meningococcemia, or occasionally gram-negative septicemia; group A streptococcal infection, heat stroke, malignant hyperthermia; extensive pump oxygenation (repair of aortic aneurysm); eclampsia, preeclampsia; tufted angioma and Kaposiform hemangioendothelioma: Kasabach–Merritt syndrome; immune complexes; postvaricella purpura gangrenosa.

• Events that complicate and propagate DIC: Shock, complement pathway activation.

Uncontrolled activation of coagulation results in thrombosis and consumption of platelets/clotting factors II, V, and VIII. Secondary fibrinolysis. If the activation occurs slowly, excess activated products are produced, predisposing to vascular infarctions/venous thrombosis. If the onset is acute, hemorrhage surrounding wound sites and IV lines/catheters or bleeding into deep tissues.

Clinical Manifestation

Hours to days; rapid evolution. Fever, chills associated with onset of hemorrhagic lesions.

Skin Lesions. Infarction (purpura fulminans) (Figs. 20-320-5): massive ecchymoses with sharp, irregular (“geographic”) borders with deep purple to blue color (Fig. 20-5) and erythematous halo, ± evolution to hemorrhagic bullae (Fig. 20-3), and blue to black gangrene (Fig. 20-5); multiple lesions are often symmetric; distal extremities, areas of pressure; lips, ears, nose, trunk; peripheral acrocyanosis followed by gangrene on hands, feet, tip of nose, with subsequent autoamputation if patient survives.

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Figure 20-3. Disseminated intravascular coagulation: purpura fulminans Extensive geographic area of cutaneous infarction with hemorrhage involving the hand. Similar lesions were on the face, the other hand, and the feet.

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Figure 20-4. Extensive cutaneous infarction with hemorrhage involving the entire leg This catastrophic event followed sepsis after abdominal surgery.

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Figure 20-5. Disseminated intravascular coagulation: purpura fulminans Geographic cutaneous infarctions on the chest; lesions were also present on the hands, elbows, thighs, and feet. The patient was a diabetic with Staphylococcus aureus sepsis.

Hemorrhage from multiple cutaneous sites, i.e., surgical incisions, venipuncture, or catheter sites.

Mucous Membranes. Hemorrhage from gingiva.

General Examination. High fever, tachycardia, ± shock. Multitude of findings depending on the associated medical/surgical problem.

Laboratory Examinations

Dermatopathology. Occlusion of arterioles with fibrin thrombi. Dense PMN infiltrate around infarct and massive hemorrhage.

Hematologic Studies. CBC. Schistocytes (fragmented RBCs), arising from RBC entrapment and damage within fibrin thrombi, seen on blood smear; platelet count low. Leukocytosis.

Coagulation Studies. Reduced plasma fibrinogen; elevated fibrin degradation products; prolonged prothrombin time, partial thromboplastin time, and thrombin time.

Blood Culture. For bacterial sepsis.

Diagnosis and Differential Diagnosis

Clinical suspicion confirmed by coagulation studies. Differential diagnosis of large cutaneous infarctions: necrosis after initiation of warfarin therapy, heparin necrosis, calciphylaxis, atheroembolization.

Course and Prognosis

Mortality rate is high. Surviving patients require skin grafts or amputation for gangrenous tissue. Common complications: severe bleeding, thrombosis, tissue ischemia/necrosis, hemolysis, organ failure.

Management

Vigorous antibiotic therapy for infections. Control bleeding or thrombosis: heparin, pent-oxifylline, protein C concentrate.

Cryoglobulinemia

ICD-9: 273.2 image ICD-10: D89.1 image

image Cryoglobulinemia (CG) is the presence of serum immunoglobulin (precipitates at low temperature and redissolves at 37°C) complexed with other immunoglobulins or proteins.

image Associated clinical findings include purpura in cold-exposed sites, Raynaud phenomenon, cold urticaria, acral hemorrhagic necrosis, bleeding disorders, vasculitis, arthralgia, neurologic manifestations, hepatosplenomegaly, and glomerulonephritis.

image Precipitation of cryoglobulins (when present in large amounts) causes vessel occlusion, also associated with hyperviscosity.

image Platelet aggregation/consumption of clotting factors by cryoglobulins, causing coagulation disorder.

image Immune complex deposition followed by complement activation and vasculitis.

Etiology and Pathogenesis

Type I Cryoglobulins: Monoclonal immunoglobulins (IgM, IgG, IgA, light chains). Associated with plasma cell dyscrasias such as multiple myeloma, Waldenström macroglobulinemia, lymphoproliferative disorders such as B cell lymphoma.

Type II Cryoglobulins: Mixed cryoglobulins: two immunoglobulin components, one of which is monoclonal (usually IgG, less often IgM) and the other polyclonal; components interact and cryoprecipitate. Associated withmultiple myeloma, Waldenström macroglobulinemia, chronic lymphocytic leukemia; rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome.

Type III Cryoglobulins: Polyclonal immunoglobulins that form cryoprecipitate with polyclonal IgG or a nonimmunoglobulin serum component occasionally mixed with complement and lipoproteins. Represents immune complex disease. Associated with autoimmune diseases; connective tissue diseases; wide variety of infectious diseases, i.e., hepatitis B, hepatitis C, Epstein–Barr virus infection, cytomegalovirus infection, subacute bacterial endocarditis, leprosy, syphilis, streptococcal infections.

Clinical Manifestation

There is cold sensitivity in <50% of cases. Chills, fever, dyspnea, and diarrhea may occur following cold exposure. Purpura also may follow long periods of standing or sitting. Due to other organ system involvement, arthralgia, renal symptoms, neurologic symptoms, abdominal pain, arterial thrombosis.

• Noninflammatory purpura (usually type I), occurring at cold-exposed sites, e.g., helix (Fig. 20-6), tip of nose.

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Figure 20-6. Cryoglobulinemia: monoclonal (type I) This noninflamed, purpuric lesion on the helix appeared on the first cold day in the fall.

• Acrocyanosis and Raynaud phenomenon, with or without severe resultant gangrene of fingertips and toes or elsewhere on arms or legs (usually type I or II) (Fig. 20-7).

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Figure 20-7. Cryoglobulinemia: mixed (type II) (A) Extensive necrosis and hemorrhage on the skin of the forearm. There was also digital gangrene on hands and feet. (B) Extensive hemorrhagic necrosis on both legs. There was also acral gangrene on four toes.

• Palpable purpura with bullae and necroses (usually types II and III) due to hypersensitivity vasculitis, occurring in crops on lower extremities with extension to thighs, abdomen; precipitated by standing up (Fig. 20-8), less commonly by cold.

• Livedo reticularis mostly on lower and upper extremities.

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Figure 20-8. Cryoglobulinemia: polyclonal (type III) Palpable purpura with widespread hemorrhagic blisters and necrosis as in any other type of hypersensitivity vasculitis (compare with Fig. 14-57). Patient had diabetes and amputation of several toes.

• Urticaria induced by cold, associated with purpura.

• Systemic involvement: Between 30% and 60% of individuals with essential mixed CG (type II) develop renal disease with hypertension, edema, or renal failure. Neurologic involvement manifests as peripheral sensorimotor polyneuropathy, presenting as paresthesias or foot drop. Arthritis. Hepatosplenomegaly.

• Diagnosis is confirmed by determination of cryoglobulins (blood drawn into warmed syringe, RBC removed via warmed centrifuge; plasma refrigerated in a Wintrobe tube at 4°C for 24–72 h, then centrifuged and cryocrit determined) and diagnosis of underlying disease.

• The course is characterized by cyclic eruptions induced by cold or fluctuations of the activity of the underlying disease.

• Treatment is that of the underlying disease.

Leukemia Cutis

ICD-9: 205.3 image ICD-10: C92.3 image

image Leukemia cutis (LC) is a localized or disseminated skin infiltration by leukemic cells. It is usually a sign of dissemination of systemic disease or relapse of existing leukemia.

image Incidence varies from <5% to 50%, depending on the type of leukemia, both acute and chronic, including the leukemic phase of non-Hodgkin lymphoma and hairy cell leukemia.

image Most commonly occurs with acute monocytic leukemia M5 and acute myelomonocytic leukemia M4.

image Most common lesions are small (2–5 mm) papules (Figs. 20-9 and 20-10), nodules (Figs. 20-11 and 20-12), or plaques. LC lesions are usually somewhat more pink, violaceous, or darker than normal skin, always palpable, indurated, firm.

image Localized or disseminated; usually on trunk (Fig. 20-9), extremities (Fig. 20-11), and face (Fig. 20-10) but may occur at any site. May be hemorrhagic when associated with thrombocytopenia or may ulcerate (Fig. 20-12). Erythroderma may (rarely) occur. Leukemic gingival infiltration (hypertrophy) occurs with acute monocytic leukemia.

image Inflammatory disorders occurring in patients with leukemia are modified by the participation of leukemic cells in the infiltrate, resulting in unusual presentations of such disorders, e.g., psoriasis with hemorrhage or erosions/ulcerations.

image Cutaneous inflammatory diseases that may be associated with leukemia are Sweet syndrome, bullous pyoderma gangrenosum, urticaria, and necrotizing vasculitis.

image Systemic symptoms are those associated with hematologic malignancy.

image The diagnosis is made by suspicion and verified by skin biopsy, immunophenotyping, and B- or T-cell receptor rearrangement studies. Hematologic studies with complete analysis of bone marrow aspirate and peripheral blood smear.

image The prognosis for LC is directly related to the prognosis for the systemic disease.

image Therapy is usually directed at the leukemia itself. However, systemic chemotherapy sufficient for bone marrow remission may not treat the cutaneous lesions effectively. Thus, a combination of systemic chemotherapy and local electron beam therapy or PUVA may be necessary for chemotherapy-resistant LC lesions.

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Figure 20-9. Leukemia cutis Hundreds of tan-pink papules and a nodule on the trunk of a female with acute myelogenous leukemia arose during a 1-week interval. Per se, these lesions are “nonspecific” and do not present a diagnosis, but when such an eruption is seen, one should perform a peripheral blood count and a biopsy.

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Figure 20-10. Leukemia cutis Multiple skin-colored and erythematous papules in a 38-year-old febrile woman that had erupted about 1 week before this picture was taken. The patient had acute myelogenous leukemia.

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Figure 20-11. Leukemia cutis A large, dark brown nodule on the upper arm of a male with acute myelogenous leukemia; six similar nodules were also present on the trunk.

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Figure 20-12. Leukemia cutis: chloroma Large, ulcerated, green-hued tumors (chloromas) in the inguinal and perineal regions of a female with acute myelogenous leukemia; similar lesions were also present in the axillae and on the tongue.

Langerhans Cell Histiocytosis

ICD-9: 202.5/277.89 image ICD-10: D76.0 image

image Langerhans cell histiocytosis (LCH) is an idiopathic group of disorders characterized histologically by proliferation and infiltration of tissue by Langerhans cell–type histiocytes that fuse into multinucleated giant cells and form granulomas with eosinophils.

image Etiology: a reactive versus neoplastic nature of LCH is debated.

image LCH is characterized clinically by cutaneous findings that range from soft-tissue swelling to seborrheic dermatitis–like changes to papular, pustular lesions, erosions, and ulcerations.

image Systemic lesions affect bones (lytic erosions), and lungs, bone marrow, liver, spleen, and lymph nodes.

image The course is variable, ranging from localized self-healing forms to generalized and fatal cases.

image Therapy depends on extent of disease and systemic involvement.

Classification

The disorders of histiocytes are classified as LCH (LCH, formerly histiocytosis X), non-LCH,1 and malignant histiocytosis. LCH is best classified as shown in Table 20-1.

TABLE 20-1 CLASSIFICATION OF LCH

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Epidemiology and Etiology

Age of Onset. Unifocal LCH. Most commonly, childhood and early adulthood.

Multifocal LCH. Most commonly, childhood.

Letterer–Siwe Disease (LSD). More commonly, infancy (LSD) and childhood. Also, adult form.

Hand–Schüller–Christian Disease (HSCD). Childhood, chronic progressive.

Hashimoto–Pritzger Syndrome (HPS). Childhood, self-healing.

Sex. Males > females.

Incidence. Rare, estimated 0.5 per 100,000 children (estimate).

Etiology and Pathogenesis

The stimulus for the proliferation of Langerhans cells is unknown. A reactive versus neoplastic nature is debated.

Clinical Manifestation

Unifocal LCH. Systemic symptoms uncommon. Pain and/or swelling over underlying bony lesion. Disruption of teeth with mandibular disease, fracture, otitis media due to mastoid involvement.

Multifocal LCH. Erosive skin lesions are exudative, pruritic, or painful and may have offensive odor. Otitis media caused by destruction of temporal and mastoid bones, proptosis due to orbital masses, loose teeth with infiltration of maxilla or mandible, pituitary dysfunction with involvement of sella turcica associated with growth retardation, diabetes insipidus. Lung involvement associated with chronic cough, pneumothorax.

LSD. Child (or very rarely an adult) is systemically ill with a course that resembles a systemic infection or malignancy. Hepatomegaly, petechiae, and purpura, generalized skin eruption.

Skin Lesions

Unifocal LCH. (Eosinophilic Granuloma)

• Swelling over bony lesion (e.g., humerus, rib, mastoid), tender.

• Cutaneous/subcutaneous nodule, yellowish, may be tender and break down, occurring anywhere.

• Sharply marginated ulcer, usually in genital and perigenital regions or oral mucous membrane (gingiva, hard palate). Necrotic base, draining, tender (Fig. 20-13).

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Figure 20-13. Langerhans cell histiocytosis: eosinophilic granuloma Solitary, ulcerated nodule with loss of teeth on the gingival ridge near the palate, associated with involvement of the maxillary bone. Lesion was asymptomatic and only when the molars were lost did the patient consult a physician.

Multifocal LCH. As in unifocal LCH; in addition, regionally localized (head) or generalized (trunk) eruptions. Papulosquamous, seborrheic dermatitis–like (scaly, oily), eczematous dermatitis–like lesions (Fig. 20-14); sometimes vesicular or purpuric (Fig. 20-15). Turn necrotic and may become heavily crusted. Removal of crusts leaves small, shallow punched-out ulcers that heal with scars. Intertriginous lesions coalesce, may be erosive and exudative, become secondarily infected, and ulcerate. Mandibular and maxillary bone involvement may result in loss of teeth (Fig. 19-13). Ulceration of vulva and/or anus (Fig. 20-16).

LSD. Skin lesions as in multifocal LCH but more widespread, disseminated (Fig. 20-15), and ulcerating in intertriginous regions (Fig. 20-16).

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Figure 20-14. Langerhans cell histiocytosis Erythema and small, orange papules with a greasy scale on the face and scalp in this infant. These were the only lesions at first presentation and were mistaken for infantile seborrheic dermatitis. After lesions proved refractory to topical treatment and additional purpuric and crusted lesions appeared on the trunk, a biopsy was performed and the correct diagnosis was established.

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Figure 20-15. Langerhans cell histiocytosis: Letterer–Siwe disease Erythematous papules and vesicles with purpura, crusting, becoming confluent on the abdomen of an infant. Some lesions have ulcerated and are crusted.

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Figure 20-16. Langerhans cell histiocytosis: Letterer–Siwe disease in an adult Confluent erythematous plaques with necrosis and ulceration in the anogenital and perineal region in a 65-year-old female.

General Findings. Multifocal LCH. Bony lesions occur in calvarium, sphenoid bone, sella turcica, mandible, long bones of upper extremities, and vertebrae. Associated findings of pituitary involvement.

HSCD. Lytic skull lesions, proptosis, diabetes mellitus, and skin lesions.

LSD. Hepatosplenomegaly, lymphadenopathy, involvement of lungs and other organs, and bone marrow; thrombocytopenia and widespread and ulcerating skin lesions (Figs. 20-15 and 20-16).

Laboratory Examinations

Histopathology. Proliferation of Langerhans cells with abundant pale eosinophilic cytoplasm and indistinct cell borders; a folded, indented, kidney-shaped nucleus with finely dispersed chromatin; epidermotropism. Langerhans cells in LCH have to be recognized by morphologic, ultrastructural (Birbeck granules), histochemical, and immunohistochemical markers [S-100 protein, CD1a, and CD207 (Langerin)].

Diagnosis

Confirmation of diagnosis by biopsy (skin, bone, or soft-tissue/internal organs). Since skin is the organ most frequently involved after bone, skin biopsies have great diagnostic significance.

Course and Prognosis

HPS. Benign, self-healing.

Unifocal LCH. Benign course with excellent prognosis for spontaneous resolution but tissue destruction.

Multifocal LCH. Spontaneous remissions possible. Prognosis poorer at extremes of age and with extrapulmonary involvement.

LSD. Commonly fulminant and fatal. Current scoring systems for evaluation of prognosis are based on number of organs involved, the presence or absence of organ dysfunction, and age. The worst prognosis is in the very young with multifocal LCH and organ dysfunction and in LSD.

Management

Unifocal LCH. Curettage with or without bony chip packing. Low-dose (300–600 rad) radiotherapy. Intralesional corticosteroids. Extraosseous soft-tissue lesions: surgical excision or low-dose radiotherapy.

Multifocal LCH. Diabetes insipidus and growth retardation treated with vasopressin and human growth hormone. Low-dose radiotherapy to bony lesions. Systemic treatment with glucocorticoids and/or vinblastine, given as single agents or in combination and etoposide. Non-responders: polychemotherapy (vincristine and cytarabine and prednisone or vincristine and doxorubicine and prednisone), cladribine (2-chlorodeoxyadenosine). Bone marrow transplantation is an option.

Cutaneous Lesions. Glucocorticoids for discrete cutaneous lesions. Also topical tacrolimus, imiquimod. Extensive or generalized: cutaneous lesions respond best to PUVA or topical nitrogen mustard but also to oral thalidomide.

Mastocytosis Syndromes

ICD-9: 757.33/202.6 image ICD-10: Q82.2 image

image Mastocytosis is an abnormal accumulation of mast cells in the skin and at various organs.

image An abbreviated WHO classification of mastocytosis is shown in Table 20-2.

image The skin is the most commonly involved organ system.

image Skin lesions are localized nodular or generalized maculopapular (Table 20-3).

image Because of the release of pharmacologically active substances, cutaneous symptoms are urticarial swelling or blistering with pruritus; systemic symptoms are blushing, vomiting, diarrhea, headache, syncope.

image Most patients with mastocytosis have only skin involvement, and most of these have no systemic symptoms. However, up to half of patients with systemic mastocytosis may not have any skin findings.

TABLE 20-2 ABBREVIATED WHO CLASSIFICATION OF MASTOCYTOSIS

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TABLE 20-3 CLASSIFICATION OF CUTANEOUS MASTOCYTOSIS (CM)

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Epidemiology

Age of Onset. Between birth and 2 years of age (55%) (NCM, PPCM, UP), but mastocytosis can occur at any age; infancy-onset mastocytosis rarely associated with systemic mastocytosis.

Sex. Slight male preponderance.

Prevalence. Unknown.

Pathogenesis

Human mast cell proliferation depends on Kit ligand and Kit is the receptor for stem cell factor. c-kit mutations have been identified in the blood and tissues of patients with mastocytosis. Mast cells contain several pharmacologically active substances that are associated with the clinical findings in mastocytosis: histamine (urticaria, GI symptoms), prostaglandin D2 (flush, cardiovascular symptoms, bronchoconstriction, GI symptoms), heparin (bleeding into tissue, osteoporosis), neutral protease/acid hydrolases (patchy hepatic fibrosis, bone lesions).

Clinical Manifestation

Stroking lesion causes it to itch and to wheal (Darier sign) (see Fig. 20-18). Various drugs are capable of causing mast cell degranulation and release of pharmacologically active substances that exacerbate skin lesions (whealing, itching) and cause flushing: alcohol, dextran, polymyxin B, morphine, codeine, scopolamine, D-tubocurarine, nonsteroidal anti-inflammatory drugs. Flushing episode can also be elicited by heat or cold and may be accompanied by headache, nausea, vomiting, diarrhea, dyspnea/wheezing, and syncope. Systemic involvement may lead to symptoms of malabsorption; portal hypertension. Bone pain. Neuropsychiatric symptoms (malaise, irritability).

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Figure 20-18. Mastocytosis: generalized (PPCM) Multiple, flat-topped papules and small plaques of brownish to yellowish color on the buttocks of a child. Lesions are asymptomatic. Rubbing one of the lesions on the left buttock has resulted in urtication and an axon flare, a positive Darier sign, and itching.

Skin Lesions (CM) Localized. NCM. Macular to papular to nodular lesions (mastocytoma) (Fig. 20-17), often solitary; may be multiple, but few. Yellow to tan-pink, which become erythematous and raised (urticate) when stroked due to degranulation of mast cells (Darier sign); in some patients, lesions become bullous.

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Figure 20-17. Mastocytosis: solitary mastocytoma (NCM) A solitary, tan plaque with poorly demarcated borders on the hand of an infant. When stroked very vigorously, the lesion became red, more elevated, and a blister developed.

Generalized. PPCM. Tan, occasionally yellowish plaques, up to 2–5 cm, sharply defined with irregular outlines. Darier sign positive (Fig. 20-18). No scaling, occasionally with bulla formation after rubbing. Occurs mostly in infants and children.

UP. Tan macules to slightly raised tan to brown papules (Fig. 20-19). Disseminated, few or >100 with widespread symmetric distribution. Darier sign (whealing) after rubbing; in infants, may become bullous. Occurs in infancy and/or de novo in adults. Bright red diffuse flushing occurring spontaneously, after rubbing of skin, or after ingestion of alcohol or mast cell–degranulating agents.

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Figure 20-19. Mastocytosis: urticaria pigmentosa (UP) (A) Multiple, generalized tan to brown papules in a child. The patient had occasional syncopes, diarrhea, and wheezing; workup revealed systemic mastocytosis. (B)Brown papules on the forehead of a 3-year-old boy who was otherwise asymptomatic.

TMEP. Freckle-like, brownish to reddish macules (Fig. 20-20) with fine telangiectasia in longstanding lesions. Hundreds of lesions, trunk > extremities; lesions may be confluent. Urticate with gentle stroking. Dermatographism. Occur only in adults and very rare.

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Figure 20-20. Mastocytosis: telangiectasia macularis eruptiva perstans Small, stellate erythematous macules and telangiectases on the back of a 45-year-old woman who had systemic (indolent) mastocytosis.

DCM. Yellowish, thickened appearance of large areas of skin; “doughy.” Smooth with scattered elevation, resembling leather, “pseudoxanthomatous mastocytosis,” skin folds exaggerated, especially in axilla/groin. Large bullae may occur after trauma or spontaneously. DCM may present as erythroderma (Fig. 20-21). Very rare, occurs at all ages.

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Figure 20-21. Mastocytosis: diffuse cutaneous mastocytosis The skin of this infant is uniformly erythematous (erythroderma) secondary to infiltrating mast cells with several spared, white areas of normal skin. In this child, there were systemic symptoms associated with the flare of erythroderma: syncope, wheezing, and diarrhea.

Laboratory Examinations

Dermatopathology. Accumulation of normal-looking mast cells in dermis. Mast cell infiltrates may be sparse (spindle-shaped) or densely aggregated (cuboidal shape) and have a perivascular or nodular distribution.

CBC. Systemic mastocytosis: anemia, leukocytosis, eosinophilia.

Blood. Tryptase levels ↑, coagulation parameters.

Urine. Patients with extensive cutaneous involvement may have increased 24-h urinary histamine excretion.

Bone Scan and Imaging. Define bone involvement (lytic bone lesions, osteoporosis, or osteosclerosis) and endoscopy for small-bowel involvement.

Bone Marrow. Smear and/or biopsy for morphology and mast cell markers.

Diagnosis

Clinical suspicion, positive Darier sign, confirmed by skin biopsy.

Differential Diagnosis

NCM. Juvenile xanthogranuloma, Spitz nevus.

Flushing. Carcinoid syndrome.

UP, PPCM, TMEP. LCH, secondary syphilis, papular sarcoid, generalized eruptive histiocytoma, non-LCH of childhood.

DCM. Cutaneous T-cell lymphoma, pseudoxanthoma elasticum, forms of erythroderma.

Course and Prognosis

Most cases of solitary mastocytosis and generalized UP and PPCM in children resolve spontaneously. They rarely have systemic involvement. Adults with onset of UP or TMEP with extensive cutaneous involvement have a higher risk for development of systemic mastocytosis (see Table 20-2). In young children, acute and extensive degranulation may be life threatening (shock).

Management

Avoidance of drugs that may cause mast cell degranulation and histamine release (see above).

Antihistamines, both H1 and H2, either alone or with ketotifen. Disodium cromoglycate, 200 mg four times a day, may ameliorate pruritus, flushing, diarrhea, abdominal pain, and disorders of cognitive function but not skin lesions. Imatinib for patients with a KIT mutation at the F522C position but ineffective with other KIT mutations. PUVA treatment is effective for disseminated skin lesions, but recurrence is common. Vascular collapse is treated with epinephrine. NCM responds to potent glucocorticoid ointments under occlusion or to intralesional triamcinolone acetonide but may eventually recur.

1For the non-Langerhans cell histiocytoses, the reader is referred to Gelmeti C and Caputo R in Wolff K et al. (eds.), Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, McGraw-Hill, 2008:1424–1434.