University of Alabama at Birmingham

Gorgas Case 2020-06

Universidad Peruana Cayetano Heredia
The following patient was seen as an inpatient at Hospital Antonio Lorena in Cusco during the Gorgas Diploma Course. We would like to thank Dr. Fatima Concha for her assistance with this case.
Image for Case 2020-06

History: A 30-year-old female patient presents with a 6-month history of illness that presents with cervical, axillary and inguinal lymphadenopathies, malaise and weight loss. One month before admission, she notices something moving in her scalp. Two weeks prior to admission, she starts noting abdominal distention.

Epidemiology: Born and lives in Manuquiari, La Convencion (Cusco), in the low jungle. Works as a homemaker and farmer. Part of the Matsiguenka native tribe. She is married. Denies previous illness. Denies any sick contacts.

Physical Examination: BP:90/60, HR 86, RR 18, afebrile. Skin and mucosae were pale. Elevated desquamative plaque in parieto-occipital area of the scalp (Image A). Painless ulcerated lesion with well defined, elevated edges and a clean base, on left knee (Image B). Painful ulcerated preauricular, postauricular and cervical lymphadenopathies, approx. 2cm in diameter, with purulent discharge (Image C). Lung examination revealed bilateral diffuse crackles. Heart auscultation was significant for a mitral systolic II/VI murmur. The abdomen was very distended, bowel sounds were present, it was dull on percussion, with a positive wave sign, with no collateral circulation. The liver was firm and markedly enlarged, with no splenomegaly. Neurological exam was normal.

Imaging StudiesChest x-ray showed a mild bilateral interstitial pattern (Image D). CT of the thorax revealed a bilateral fine ground-glass pattern, predominantly in bases, and mediastinal adenopathies (Image E). Abdominal ultrasound revealed an enlarged liver and abundant free fluid. Abdominal CT showed hepatomegaly, ascites and periaortic adenopathies (Image F).

Laboratory: Hb: 6 g/dL; Hct. 22%; WBC 11 540 (neutrophils: 90%, eosinophils: 2.95%, lymphocytes: 4.07%); Platelets: 374 000. INR 1.4, PT 19.7, PTT 40.5. Gluc: 90 mg/dL, Urea: 39 mg/dL, Creat: 0.38 mg/dL, AST 15, ALT 10, GGT 15, Alk Phos 98, total bilirubin 0.23 (direct 0.07), LDH 196, albumin 2.1. AFB in sputum, urine, feces, lymphadenopathy secretion: negative. HIV and HBsAg were non-reactive. VDRL negative.

Notes: Five different pathogens were isolated from this patient.


UPCH Case Editors: Carlos Seas, Course  Director / Alvaro Schwalb and Paloma Carcamo, Associate Coordinators

UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

 

Diagnosis: Disseminated paracoccidioidomycosis, kerion (tinea capitis), myiasis, cutaneous leishmaniasis, intestinal hookworm infection.

Images for Case 2020-06
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Discussion: Direct microscopy with 10% KOH of secretion from the lymphadenopathies showed large oval yeast cells surrounded by budding daughter yeast cells, characteristic for Paracoccidioides spp (Image G). Direct microscopy of skin scrapings from the scalp lesion revealed multiple arthroconidia, making the diagnosis of tinea capitis. The patient had had fly larvae removed from this same lesion in the scalp prior to presentation in the hospital. Direct microscopy of skin scraping from the knee revealed abundant Leishmania sp. amastigotes (Image H). Direct microscopy of the stool revealed oval thin-shelled ova with blastomeres inside, corresponding to hookworm eggs (Image I). Baermann test for S. stercoralis was negative.

Paracoccidioidomycosis, also known as South American Blastomycosis, is a systemic fungal disease caused by Paracoccidioides brasiliensis and Paracoccidioides lutzii. It is endemic in the Americas, between the latitudes of 23°N and 23°S. Most reported cases occur in Brazil, with some reports from Colombia, Venezuela, Argentina, and Ecuador (https://www.ncbi.nlm.nih.gov/pubmed/29371520). There is scarce information about this disease in Peru, but all reported cases have a history of exposure to the high or low jungle (http://www.scielo.org.pe/scielo.php?pid=S1726-46342002000100009&script=sci_arttext).

Paracoccidioides spp. is a thermally dimorphic fungus, found in its mycelial form in soil and decaying vegetation. At body temperature, the fungus turns into yeasts, which can be seen as 4-40 μm oval budding cells. The two typically described structures on microscopic observation are the “boat steering wheel” conformation of a mother cell surrounded by blastoconidia, and the “Mickey Mouse ears”, a mother cell with two budding cells. This is in contrast to the round to oval multinucleate yeast cell with a single broad-based bud that is characteristic of Blastomycosis (https://cmr.asm.org/content/23/2/367). Reservoirs for this pathogen include humans and armadillos. Yeast forms may be found in biopsy samples of any affected organs, scrapings of superficial lesions, sputum samples, or in abscess or lymph node aspirates. Direct microscopy with KOH is positive in about 90% of cases, but samples can also be cultured in Sabouraud’s agar to increase diagnostic yield. Cultures usually take 20 to 30 days to grow, and may not be useful in informing timely clinical decision-making, and treatment should be started with direct microscopy findings. Serologies are useful as screening tests, but may cross-react with other dimorphic fungi, such as Histoplasma capsulatum (https://www.ncbi.nlm.nih.gov/pubmed/18380607).

Infection typically starts with inhalation of conidia. In a few patients, disease may occur a short time after infection (acute paracoccidioidomycosis). However, in most cases, the fungus remains in quiescent foci that can reactivate many years after primary infection, causing the chronic form of the disease. In endemic areas, it is estimated that up to 75% of the adult population may be infected, but only a few will show symptoms of the disease.

Disseminated paracoccidioidomycosis refers to disease involving multiple organ systems, as in the case of our patient. It is typically described in immunosuppressed hosts, usually HIV patients, solid organ transplant recipients, or patients with malignancies (https://www.ncbi.nlm.nih.gov/pubmed/15057336). Paracoccidioides coinfection with HTLV-1 has not been well studied, but has been previously reported in Peru, and appears to predispose to more severe disease and coinfection with multiple pathogens, as seen with our patient (https://www.ncbi.nlm.nih.gov/pubmed/20560735). Unfortunately, testing for HTLV is not widely available in Cusco and the patient could not be tested.

The more common presentation is chronic paracoccidioidomycosis (CoW 2017-08, 2013-05), seen in adults between 40 and 60 years of age. Patients initially present pulmonary manifestations such as cough and dyspnea, and are often misdiagnosed with tuberculosis. Later symptoms include granulomatous or ulcerated mucocutaneous lesions (especially in mouth and nasopharynx), and occasionally central nervous system involvement. Acute or juvenile paracoccidioidomycosis is an uncommon form and it is typically seen in children, adolescents and immunosuppressed adults (CoW 2010-07, 2006-02). It presents with fever, anorexia, asthenia and malaise. Respiratory and mucocutaneous manifestations are not regularly seen. Because of rapid dissemination of the pathogen to the reticuloendothelial system, physical examination often reveals generalized adenopathies, subcutaneous nodules, hepatosplenomegaly, and sometimes bone involvement. Differential diagnoses for this clinical presentation of Paracoccidioides spp. infection include histoplasmosis, tuberculosis, syphilis, and lymphoma.

The treatment of choice for most cases of paracoccidioidomycosis is itraconazole at doses of 100-200 mg/day. In patients with severe disease or central nervous system involvement, treatment should be started with amphotericin B deoxycholate, and can be switched to an oral agent after clinical improvement. Treatment should be continued until there is substantial clinical and radiological evidence of improvement or resolution of symptoms, usually after 6 to 12 months. About 5% of patients may relapse, especially if they had disseminated disease (https://www.ncbi.nlm.nih.gov/pubmed/18380607). Our patient received a course of treatment with albendazole, and is currently receiving amphotericin B deoxycholate, with moderate improvement.

Regarding the other diagnoses, leishmaniasis is endemic in the area where the patient lives. The most commonly isolated species in the area is L. braziliensis, which raises concerns for mucous membrane involvement. Pentavalent antimonials are the first-choice therapy, but if it is not available, amphotericin B can also be used. After completing treatment, our patient needs to be periodically monitored for relapses - ideally, every three months for at least one year.

Myiasis refers to the infestation of fly larvae in human tissue, and can be primary, if the larvae invades intact skin, or secondary, if it infects damaged skin (as seen with our patient, who had myiasis over a kerion). The most frequently described species in Peru are Cochliomyia hominivorax and Dermatobia hominis (CoW 2004-06, 2005-06, 2008-06). Removal of larvae is curative, although some cases may require antibiotic therapy for bacterial superinfection.

There are two major species of hookworm that may infect humans: Ancylostoma duodenale, in Europe and Asia, and Necator americanus, in the Americas, Africa, and some parts of Asia. Their eggs are indistinguishable. Infection with hookworm may cause cutaneous larva migrans upon dermal penetration of the parasite, some coughing and pharyngeal irritation as the parasite passes through the lungs, and nausea, vomiting, diarrhea, or abdominal pain when the larvae migrate to the small intestine. Chronic infection may cause anemia due to blood loss when the worms attach to the intestinal mucosa. Diagnosis is made by observation of eggs on stool examination; the standard method is the Kato Katz technique. Treatment consists of albendazole 400mg daily for three days; alternatives include mebendazole and pyrantel pamoate. Single doses of albendazole are used in public health programs. There is scant evidence about the benefit of regular deworming of groups at risk without evidence of infection (https://www.ncbi.nlm.nih.gov/pubmed?term=26202783).