Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 13-2

Two-Year-Old Girl

STEPHEN LUDWIG

BRANDON C. KU

HISTORY OF PRESENT ILLNESS

The patient is a 2-year-old Vietnamese girl who has been well until her mother noted a bump under her jaw a few days ago. She has not had any fever or upper respiratory tract symptoms (cough, rhinorrhea), or sore throat. She has been acting well. The bump does not hurt, is not red, but during the last 2-3 days it has increased in size from pea-sized to 4-5 cm, and it now looks purple. She had normal oral intake and urine output. There was no vomiting, diarrhea, or rash. The patient sweats at night, but this is not new. There has been no weight loss or change in appetite. Sleep pattern is normal. There was no history of animal bites. There was no dyspnea or wheezing.

MEDICAL HISTORY

The girl was born at term by spontaneous vaginal delivery without complications. She had pyelonephritis twice, once at 14 months of age and again at 16 months of age. A voiding cystourethrogram performed after the second episode of pyelonephritis revealed grade 3 vesicoureteral reflux. She did not have frequent upper respiratory infections, otitis media, or pneumonia. She has not had any skin or soft tissues infections. Her only medication was trimethoprim-sulfamethoxazole which she received as prophylaxis against urinary tract infections. She has received her routinely recommended immunizations, including measles, mumps, rubella, and varicella vaccination at 15 months of age. She has no known allergies. There is no family history of recurrent infections, immune dysfunction or autoimmune disease. The patient lives with parents in a semi-rural area of New York state. Her maternal grandmother assists with childcare. No family members or recent visitors have been incarcerated or live or work in nursing homes or other chronic care facilities. The family does not have any pets. The only animal with whom the child interacts is an older cat owned by a maternal aunt who lives nearby.

PHYSICAL EXAMINATION

T 36.0°C axillary; HR 108; RR 22; BP 121/60; Weight 12.8 kg (30th percentile); Height 91 cm (30th percentile); Head Circumference 48.1 cm (25th percentile)

On general examination, the patient was alert, well nourished, and well developed. She cooperated with the examination in a manner appropriate for her age. She had a 3 × 2 cm firm nodule with purplish hue of overlying skin at the angle of the right mandible (Figure 13-2). It was not tender. There was no overlying warmth or discharge. There were no cardiac murmurs or rubs. The lungs were clear to auscultation bilaterally. With the exception of the neck, there were no masses or enlarged lymph nodes elsewhere.

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FIGURE 13-2. Neck mass in the patient (Case 13-2).

DIAGNOSTIC STUDIES

Hemoglobin, 13 g/dL; platelets, 210000/mm3;

WBC count, 6400/mm3 (45 segmented neutrophils, 46 lymphocytes, 8 monocytes); sodium, 139 mEq/L; chloride, 100 mEq/L; blood urea nitrogen, 17 mg/dL; glucose, 84 mg/dL; PT, 12.8; PTT, 31.9 seconds; phosphorous, 4.5 mg/dL; calcium, 8.2 mg/dL; magnesium, 1.6 mg/dL; cat-scratch titers, <1:32.

COURSE OF ILLNESS

The primary pediatrician initiated treatment with oral amoxicillin-clavulanate with an increase in the size of the mass over 2 weeks. Therefore, the antibiotic regimen was changed to clindamycin without any substantive change in the lymph node after 1 week. Tuberculin skin testing by purified protein derivative resulted in a 10-mm area of induration. A chest X-ray (Figure 13-3) revealed additional findings that prompted an excisional biopsy of the lymph node and bronchoscopy.

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FIGURE 13-3. Chest radiograph.

DISCUSSION CASE 13-2

DIFFERENTIAL DIAGNOSIS

The patient was characterized by having an increased neck mass. The mass in this case did not hurt. This differential is from an acute adenoiditis with a usual bacterial organism. The location of the mass was over the mandible in a position typical for a lymph node. The patient was treated with antibiotics without response. The chest radiograph revealed bilateral mediastinal lymphadenopathy (Figure 13-3). A chest CT confirmed hilar lymphadenopathy but did not identify any focal lung abnormalities. She was admitted for excisional biopsy of the lymph nodes of the neck and bronchoscopy.

Lymph node pathology revealed necrotizing granulomas consistent with atypical mycobacterial infection. In addition, there were two other findings of importance, a positive PPD and positive chest radiograph. These findings required that a tissue diagnosis be made and so the patient was sent for biopsy and bronchoscopy after less invasive diagnostic studies failed to reveal an etiology. The pathology showed a pattern consistent with atypical mycobacterial infection. This was also consistent with the child’s course of an acute enlargement of a lymph node but not the signs of an acute bacterial infection. There was no history of trauma. The location of the mass was not usual for a congenital lesion.

DIAGNOSIS

Nontuberculous mycobacterial infection causing adenitis in neck and mediastinum. There was no underlying immunodeficiency found in this patient.

INCIDENCE AND EPIDEMIOLOGY OF ADENITIS

Most cases of mycobacterial adenitis in children are usually caused by nontuberculosis mycobacteria rather than Mycobacterium tuberculosis. Nontuberculous mycobacteria typically include M. abscessus, M. chelonae, M. fortuitum, M. avium complex, and M. kansasii. They are typically found in soil and water, including natural and treated water sources.

CLINICAL MANIFESTATIONS

Cervical or submandibular adenitis most commonly occurs in otherwise healthy children 1-5 years of age. The likely mechanism is ingestion of contaminated sources such as soil. Mycobacterium aviumcomplex is identified most often. The presentation is protracted lymphadenopathy; the affected lymph nodes are usually unilateral and nontender. In the absence of effective therapy, the affected lymph nodes may resolve or progression to liquefaction with violaceous discoloration of the overlying skin, followed by spontaneous and prolonged drainage from a cutaneous fistula. Nontuberculous mycobacteria may also involve other lymph node groups, including the mediastinal lymph nodes as in this case. In the chest, the findings are relatively silent and relate primarily to enlargement of paratracheal lymph nodes.

DIAGNOSTIC APPROACH

In this case, the diagnosis was strengthened by findings of enlarged mediastinal nodes and the notation of a positive PPD.

Tuberculin skin testing. Tuberculin skin tests (i.e., purified protein derivative) may be negative or positive. Many children have intermediate induration (5-10 mm) though up to one-third of affected children may have induration more than 10 mm. In this case, although there was strong suspicion for nontuberculous mycobacteria, there was the need to confirm the diagnosis with biopsy or bronchoscopy findings.

Biopsy. As much material as possible is required; swabs typically have poor yield. The specimens should be placed in both broth and solid media. Cultures in broth media have a higher yield and tend to produce more rapid results than specimens plated on solid media; solid media, however, permit observation of colony morphology and recognition of multiple mycobacterial species. Excisional biopsy is often performed for simultaneous diagnosis and treatment.

TREATMENT

The treatment in cases of atypical mycobacteria is lymph node excision. Many nodes may regress on their own if untreated. However, the need to establish a diagnosis usually prompts excision. If excision is not possible because of location (e.g., facial nerve injury may occur with excision of preauricular lymph nodes), antimicrobial therapy may be beneficial. Treatment depends on the nontuberculous mycobacteria isolated. Treatment typically involves at least two effective drugs. Empiric therapy, while awaiting culture and susceptibility results, often includes clarithromycin in combination with rifabutin, rifampin, ciprofloxacin, or ethambutol. A randomized trial compared a “wait-and-see” approach with 12-weeks of clarithromycin plus rifabutin; eligible patients all had red, fluctuant lymphadenitis. The median time to resolution of disease (defined as a 75% or greater reduction in lymph node size with cured fistula and total skin closure without recurrence) was 36 weeks for the treated group and 40 weeks for the “wait-and-see” group.

SUGGESTED READINGS

1. Altman RP, Margileth AM. Cervical lymphadenopathy from atypical mycobacteria: diagnosis and surgical treatment. J Pediatr Surg. 1975;10:419-422.

2. Dhooge I, Dhooge C, DeBaets F, et al. Diagnostic and therapeutic management of atypical mycobacterial infections in children. Euro Arch Oto-Rhin-Laryngol. 1993;250:387-391.

3. Benson-Mitchell R, Buchanan G. Cervical lymphadenopathy secondary to atypical mycobacterial in children. J Laryngol Otolo. 1996;110:48-51.

4. Danielides V, Patrikakos G, Moerman M, et al. Diagnosis, management and surgical treatment of non- tuberculous mycobacterial head and neck infection in children. J Oto-Rhino-Laryngol. 2002;64:284-289.

5. Scott CA, Atkinson SH, Sodha A, et al. Management of lymphadenitis due to non-tuberculous mycobacterial infection in children. Pediatr Surg Int. 2012;28: 461-466.

6. Tortoli E. Clinical manifestations of nontuberculous mycobacteria infections. Clin Microbiol Infect. 2009;15:906-910.

7. Clark JE. Nontuberculous lymphadenopathy in children: using evidence to plan optimal management. Adv Exp Med Biol. 2011;719:117-121.

8. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial disease. Am J Resp Crit Care Med. 2007;175:367-416.

9. Hazra R, Robson CD, Perez-Atayde AR, Husson RN. Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy. Clin Infect Dis. 1999;28:123-129.

10. Lindeboom JA. Conservative wait-and-see therapy versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children. Clin Infect Dis. 2011;52:180-184.