The Gorgas Courses in Clinical Tropical Medicine

Selected Cases Seen by 2007 Course Participants

Discussion:  Histology of the cervical lymph node disclosed granulomatous lymphadenitis with extensive areas of necrosis and multiple yeast forms characteristic of P. brasiliensis [Image C from the Gorgas Course case files represents similar histology].  PAS staining also demonstrated yeast forms compatible with paracocciodomycosis.  Ziehl-Nielsen stain was negative.

We have recently presented a case of mucocutaneous leishmaniasis [2006 #5] and will not discuss that infection in detail further here, but focus on the pulmonary disesase.  The major differential diagnosis in Peru of oro-pharyngeal lesions in non-HIV infected patients would be mucosal leishmaniasis, paracoccidiomycosis, carcinoma, or lymphoma.  In Peru leishmaniasis would be by far the most common.  The spread to the larynx and vocal cords is consistent only with leishmaniasis.  In general, oral lesions of paracoccidomycosis are painful, are frequently friable and bleed on contact, and gingival and buccal mucosa are frequently involved.

The differential diagnosis for the lung disease includes: TB, histoplasmosis, lymphoma, cancer and cryptococcosis.  The most typical radiographic pattern of paracoccidomycosis is bilateral mixed infiltrates (alveolar and interstitial), mainly located in the middle and lower lobes.  Interstitial lesions may have a miliary, nodular or fibronodular patterns.  Other patterns observed in these patients are hilar and mediastinal lymph node enlargement, cavities, and calcified lesions.  Our patient has advanced disease and almost all of these findings on CT scan of the lung [Image D].

Extrapulmonary disease is found in over 70% of cases and may involve skin, mucous membranes, lymph nodes, adrenals, abdominal organs and CNS (in 10%).  Bacterial superinfection of ulcerative oral lesions when they occur is more common than with oral ulcers due to mucocutaneous leishmaniasis.  This case is representative of the chronic form (adult type) of the disease, which is believed to represent reactivation of latent infection.  This type represents approximately 94% of all cases in the experience at our institute (94 patients, up to 2001), and approximately 85% in the Brazilian series [Rev Soc Bras Med Trop. 2003;36(4):455-9].  In our experience the male:female ratio in chronic paracocciodomycosis is 20:1.  As in this case, TB coexists in up to 10% of patients with paracoccidiomycosis.  Cavitation and pleural effusion are less commonly seen than in TB.  The negative acid fast stains during the current hospitalization after 1 month of therapy would not be consistent with MDR TB.

Paracoccidiomycosis, also known as South American blastomycosis is found in humid forested or lush green areas of the Americas from Southern Mexico south to Uruguay and Argentina.  It appears to be most common in Brazil.  The exact habitat of the organism is unclear but transmission is described as being entirely by airborne inhalation.  However, we have observed cases with only oral lesions apparently associated with the use of tree leaves contaminated with fungal spores as toothpicks.  Primary pulmonary infection may be asymptomatic and self-limited but even with treatment will produce at least moderate pulmonary fibrosis.  Rural adult male agricultural workers between 30-60 years of age are most affected by the infection.  Travelers spending less than 6 months in an endemic area are unlikely to acquire paracoccidiomycosis.

Sulfonamides, ketoconazole, itraconazole, and amphotericin B are all effective therapies.  Amphotericin should be reserved for severe cases.  Itraconazole 100-200 mg/day for 6-9 months is regarded as the treatment of choice when it is available and affordable.  Relapses are common with less than 6 months therapy and expert opinion is now that 1 year is not necessary.  In the developing-world setting, ketoconazole is likely equally effective and is usually less than half the cost.  However, 12 months of therapy with ketoconazole is generally recommended.

In severe cases with a high yeast burden such as in our case, the practice is to induce such patients with amphotericin B for at least 10 days, then switch to oral itraconazole 200 mg per day, to complete a total duration of at least 9 months.  As amphotericin B for 28 days is the therapy of choice for mucosal leishmaniasis that has developed despite previous treatment of cutaneous disease with antimony, our patient was begun on 0.5 mg/kg per day.  The TB therapy is continuing.

History:  52 year old male who presented with a 4 month history of fever, night sweats, dyspnea, dry cough and a 25 kg weight loss.  He also reports increasing hoarseness and increasing pain on swallowing.  Initial sputum examination for acid-fast bacilli was negative, but 1 month prior to admission he presented at a hospital in another city and was diagnosed with sputum positive TB [chest X-ray shown in Image A] and begun on standard 4-drug therapy with which he was adherent.  At the time of admission he reports continued progression of his symptoms and weight loss.

Epidemiology:  Patient is a farmer from Quillabamba in the jungle regions of Cusco Department.  Non-smoker, non-drinker, no previous TB history.  Was treated with an unknown quantity of antimony 15 years ago for a cutaneous leishmania ulcer on his chest wall.

Physical Examination:  Afebrile.  Normal vital signs.  2 cm non-tender right cervical lymph node.  Direct laryngoscopy disclosed a granulomatous appearing lesion on the true vocal cords.  Examination of the chest disclosed no evidence of pleural effusion or consolidation.  There were bronchial breath sounds bilaterally but worse at the right base.  No hepatosplenomegaly.  Skin:  quiescent psoriasis most marked on the legs, scar of previous leishmanial ulcer.

Laboratory Examination:  Hematocrit 35.  WBC 16.7 with 70 neutrophils, 4 bands, 3 eosinophils, 21 lymphs.  LFTs normal.  BUN, creatinine normal.  HIV negative.  HTLV-1 negative.  3 induced sputum samples for acid fast bacilli and PAS staining negative.  Chest X-ray soon after admission and after over 1 month of anti-TB medication is shown in Image B.  Vocal cord biopsy was positive for Leishmania but as this did not explain the progressive pulmonary disease, a lymph node biopsy was performed.