histoplasmosis

Chest Pain, Weakness, and Weight Loss in a 13-Year-Old Girl

Kristin E. Herbert, DO, MPH

A 13-year-old girl presented to a Florida emergency department  with concern about chest pain, weakness, and weight loss. She described right-sided, pressure-like pain on expiration with a severity of 5 on a 10-point scale. She reported having had tachycardia for 1 week, dizziness upon standing for 1 month, and a 7-pound weight loss over the past 2 weeks. She had gone camping in Ohio 1 month prior. She denied fever, cough, congestion, vomiting, or diarrhea.

Physical examination revealed an alert, nontoxic-appearing adolescent in no acute distress. Vital signs were as follows: weight, 47 kg; temperature, 36.5°C; pulse, 70 beats/min; respiratory rate, 20 breaths/min; blood pressure, 104/65 mm Hg; and oxygen saturation, 99% on room air. Her lungs were clear to auscultation bilaterally. The rest of the examination findings were normal.

Results of a complete blood count, a complete metabolic panel, and C-reactive protein testing were within normal limits. The erythrocyte sedimentation rate was mildly elevated at 28 mm/h (reference range, 0-20 mm/h), as was the lactate dehydrogenase level, at 292 U/L (reference range, 84-246 U/L).

Chest radiography and contrast-enhanced computed tomography (CT) imaging were performed; axial and coronal CT images are shown in Figures 1 and 2, respectively.

What is causing these symptoms?

A. Sarcoidosis
B. Histoplasmosis
C. Small cell carcinoma of the lung
D. Non-Hodgkin lymphoma

(Answer and discussion on next page)

Answer: B, histoplasmosis

The chest radiograph showed an asymmetric enlargement of the left hilum, suggesting lymphadenopathy, and a prominent right mediastinum. The chest CT images (Figures 1 and 2) showed mediastinal lymphadenopathy, with a 2.4 × 1.6-cm right lower paratracheal lymph node and a 1.5 × 1.7-cm subcarinal lymph node; bilateral hilar lymphadenopathy; pulmonary nodules measuring 7 mm and 5 mm in the right upper lobe; a 4-mm nodule in the right middle lobe, and multiple small nodules in the left upper lobe and the left middle lobe.

The girl was admitted to the pediatric inpatient unit. The results of an oncology workup for various tumor markers, an immunology workup, and an infectious disease workup for tuberculosis, blastomycosis, coccidioidomycosis, and aspergillosis were negative.

Tests for histoplasmosis were performed, the results of which were as follows:

Histoplasma capsulatum mycelial complement-fixation (CF) antibody assay, 1:32 titer (negative result, < 1:2), H band present (indicating active infection)

Histoplasma yeast CF antibody assay, 1:64 (negative result, < 1:2), H band present

Histoplasma mycelial immunodiffusion antibody assay, positive

• Serum Histoplasma antibody assay, 1:4 (negative result, < 1:1)

• Serum Histoplasma antigen assay, 0.39 EU (negative result, < 5.5 EU)

• Urine Histoplasma antigen assay, 4.32 EU (equivocal results, 3.51-4.5 EU; positive result, > 4.5 EU)

The patient received a diagnosis of mediastinal adenitis caused by histoplasmosis. She was treated as an outpatient with itraconazole for 6 weeks and had complete resolution of her chest pain and weakness. Repeated chest CT showed almost complete resolution of her mediastinal lymphadenopathy and pulmonary nodules.

Discussion

Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus. In the United States, cases of histoplasmosis typically present in the Ohio River Valley and Mississippi River Valley.1,2 Infection is caused by inhalation of fungal spores found in the soil, bird droppings, or bat guano.1,2 Persons whose activities involve caves, decaying trees, mining, farming, or demolition are at greater risk.2 The incubation period typically is 1 to 3 weeks from the time of exposure.2

Histoplasmosis is symptomatic only in 5% of cases.2 Symptoms of acute infection can include fever, headache, chest pain, cough, and myalgia.1 Less frequent symptoms include weight loss, pericarditis, pericardial effusions, and severe respiratory distress requiring intubation.1 The severity of infection depends on the initial inoculum size, the inherent virulence of the Histoplasma strain, and the immune status of the host.3

Antibody titers of 1:32 or greater to the pathogenic yeast phase and the nonpathogenic mycelial phase of the 2 clinical isolates of H capsulatum are diagnostic evidence of active or recent infection.1-3

Antigen detection in serum and urine is most sensitive in cases of severe, acute pulmonary infection or progressive disseminated infection. However, negative results for Histoplasma antigen in urine and serum does not exclude infection.2 In the case presented, the patient’s serum and urine antigen test results were negative, but both the mycelial-phase and yeast-phase titers were 1:32 or greater, indicating an active infection.

Treatment with amphotericin B is indicated for severe or disseminated infections, and itraconazole is indicated for mild to moderate infections that meet certain criteria.1,2,4 Recommendations from the American Academy of Pediatrics2 and the Infectious Diseases Society of America4 state that antifungal treatment of mediastinal lymphadenitis is unnecessary unless corticosteroid treatment is needed due to obstruction or if the patient’s symptoms last more than 1 month.2,4 Moreover, persistent fevers, fatigue, and weight loss raise concern for the development of progressive disseminated histoplasmosis, and antifungals should be initiated in patients with these signs and symptoms.4 In the case described here, the patient was treated with itraconazole in response to her chest pain lasting more than 1 month, her weight loss, and her fatigue.

Kristin E. Herbert, DO, MPH, is a third-year pediatric resident at Palms West Hospital, with the Palm Beach Consortium for Graduate Medical Education, in Palm Beach County, Florida.

References

1. Gould JM, Aronoff SC. Histoplasmosis (Histoplasma capsulatum). In: Kliegman RM, Stanton BF, St. Geme JW III, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:1062-1064.

2. Histoplasmosis. In: American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012: 409-411.

3. Edwards, JA, Chen C, Kemski MM, Hu J, Mitchell TK, Rappleye CA. Histoplasma yeast and mycelial transcriptomes reveal pathogenic-phase and lineage-specific gene expression profiles. BMC Genomics. 2013;14:695.

4. Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7):807-825.