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Year : 2019  |  Volume : 62  |  Issue : 3  |  Page : 512-513
Sequential surprises; Non endemic mycoses revealing immunodeficiency

1 Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala, India
2 Department of Microbiology, M.E.S. Medical College, Perinthalmanna, Kerala, India

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Date of Web Publication26-Jul-2019

How to cite this article:
Abdulla MC, Mustaq S, Narayan R. Sequential surprises; Non endemic mycoses revealing immunodeficiency. Indian J Pathol Microbiol 2019;62:512-3

How to cite this URL:
Abdulla MC, Mustaq S, Narayan R. Sequential surprises; Non endemic mycoses revealing immunodeficiency. Indian J Pathol Microbiol [serial online] 2019 [cited 2021 Sep 28];62:512-3. Available from: https://www.ijpmonline.org/text.asp?2019/62/3/512/263500


Histoplasmosis is an under-recognized disease in India which should be considered in the differential diagnosis of patients with prolonged fever and granulomatous disease on histopathology without response to anti tubercular drugs.[1]

A 34 year old male, an auto-rickshaw driver was admitted with high grade fever and cough with mucoid sputum for two months. He denied history of weight loss, high risk behaviour, overseas travel (Central and South America, Africa and Australia), contact with pets or wild animals, had no sick contacts, and had no history of addictions. On examination he had enlarged cervical lymphnodes which were discrete and non tender, high-grade fever and fine inspiratory crepitations in the left infra axillary and infra scapular areas.

Chest X-ray showed left lower lobe consolidation. HIV, hepatitis B and hepatitis C serologies were negative. Blood and sputum cultures were sterile. Sputum for acid fast bacilli was negative. Contrast enhanced computed tomogram of thorax showed left lateral basal segment consolidation [Figure 1]. Gram stain, acid fast bacilli staining and fungal stain of bronchial washings and bronchio alveolar lavage were negative. Fungal, bacterial and mycobacterial culture of bronchial washings and bronchio alveolar lavage yielded no growth. Cervical lymph node biopsy showed suppurative granulomatous lymphadenitis. GeneXpert test for tuberculosis was negative. Work up for other causes of granulomatous lymphadenitis including serology for brucellosis, serum angiotensin converting enzyme level and C and P anti-neutrophil cytoplasmic antibodies were negative. He was started on anti tubercular drugs empirically considering tuberculosis as the likely cause for granulomatous lymphadenitis and left lower lobe consolidation, even though the tests were negative. After six months of anti tubercular drugs he developed two swellings over the scalp.
Figure 1: Contrast enhanced computed tomogram of thorax showing left lateral basal segment consolidation

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He had occasional fever, cough and loss of weight during the six months. Repeat physical examination showed two soft, fluctuant and tender scalp swellings (5 × 4 cm and 1 × 2 cm) with bilateral infra axillary and infra scapular fine crepitations. Hemoglobin was 9.8 g/dl total leucocyte count 23,400/mm3 with 84% neutrophils, platelet count 4, 69,000/mm3, erythrocyte sedimentation rate 99 mm in 1 h and c reactive protein was 18 (normal range <6.0 mg/L). Chest X-ray showed bilateral lower lobe consolidation. Ultra sonography of abdomen showed mild hepatosplenomegaly. Repeat contrast enhanced computed tomogram of thorax showed consolidation in right upper, mid, and bilateral lower lobes with multiple mediastinal, subcarinal and paratracheal lymph nodes.

The pus from the scalp abscess was drained and the abscess wall histopathology revealed intracellular oval shaped fungal organisms with narrow-based budding morphologically consistent with histoplasmosis [Figure 2]a and [Figure 2]b. Culture of pus on Sabouraud's dextrose agar showed growth of dimorphic fungus (yeast form at 37°C and mould at 22°C) after 5 weeks. He was diagnosed to have disseminated histoplasmosis. Work up for an underlying immunodeficient state revealed chronic granulomatous disease (dihydrorhodamine tests showed no uptake in neutrophil oxidative burst after phorbol myristate acetate stimulation). The patient was initially treated with liposomal amphotericin B for 14 days at a dose of 3 mg/kg followed by itraconazole 200 mg twice daily. When reviewed after 2 months he was afebrile, had no cough and the scalp swellings disappeared.
Figure 2: (a) Small oval narrow-based budding yeast in the pus from scalp abscess. (b) Histopathology of abscess wall revealing small oval narrow-based budding yeast morphologically consistent with histoplasmosis (40x, H and E staining)

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Differential diagnosis for a man with granulomatous lymphadenitis and unresolving pneumonia with new onset swellings over the scalp include a variety of infectious and non infectious causes. Differential diagnosis of granulomatous disease are classified into infections, vasculitis, immunological aberration, leucocyte oxidase deficiency, hypersensitivity, chemicals, and neoplasia. Infectious granulomatous lymphadenitis can be classified into suppurative lymphadenitis and nonsuppurative lymphadenitis. Tularemia, cat scratch disease, yersinia and lymphogranuloma venereum results in suppurative lymphadenitis. Non suppurative granulomatous lymphadenitis can be due to mycobacterium tuberculosis, nontuberculous mycobacteria, toxoplasma, syphilis and brucellosis. Fungal infection (Cryptococcus, Histoplasma, Coccidioidomycosis, Pneumocystis) can cause suppurative and non suppurative granulomatous lymphadenitis.[2]

Our patient had granulomatous lymphadenitis and left lower lobe consolidation initially and the tests for granulomatous disorders including bacteria, mycobacteria, fungi and other non infectious causes were negative. Though tests for diagnosis of tuberculosis were negative, condiering the high disease burden across the country, patient was empirically started on anti-tuberculosis treatment. When he presented with new manifestations (scalp swellings) and worsening of pneumonia a diagnosis of disseminated histoplasmosis with chronic granulomatous disease was made by appropriate tests. Granulomatous lymphadenitis in our patient may be secondary to either histoplasmosis or chronic granulomatous disease itself.

Diagnosis of histoplasmosis can be made from culture and histopathology. Other methods include antigen detection, polymerase chain reaction assays and antibody tests.[3],[4] Histopathology is the prime investigative modality, as identification of histoplasma organism in the section provides conclusive evidence of the disease. Skin lesions of histoplasmosis include papules and plaques with or without crusts, pustules and nodules to mucosal ulcers and erosions, molluscum contagiosum-like lesions, acneiform eruptions, erythematous papules and keratotic plaques.[5]

Among the forms of histoplasmosis reported from India, disseminated histoplasmosis is the rarest.[6] The clinical features of disseminated form of histoplasmosis are fever, malaise, anorexia, and weight loss, hepatosplenomegaly, lymphadenopathy, pallor and petechiae if pancytopenia is present and mucocutaneous lesions.[4] Patients with defective cell-mediated immunity against the organism are likely to manifest symptomatic disease during the period of acute dissemination including patients with AIDS, transplant recipients, hematologic malignancies, and corticosteroids usage. Chronic granulomatous disease is an immunodeficiency syndrome involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens. Infections in such patients are commonly due to staphylococcus aureus, pseudomonas species, nocardia species, and fungi (such as Aspergillus species and Candida albicans).[6]

To conclude, in non-endemic areas like India, where clinical suspicion is low the correct diagnosis of disseminated histoplasmosis is difficult. Disseminated fungal infections should prompt the treating physician to look for an underlying immunodeficient state.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Gopalakrishnan R, Nambi PS, Ramasubramanian V, Abdul Ghafur K, Parameswaran A. Histoplasmosis in India: Truly uncommon or uncommonly recognised? J Assoc Physicians India 2012;60:25-8.  Back to cited text no. 1
James DG. A clinicopathological classification of granulomatous disorders. Postgrad Med J 2000;76:457-65.  Back to cited text no. 2
Stevens DA. Diagnosis of fungal infections: Current status. J Antimicrob Chemother 2002;49 Suppl 1:11-9.  Back to cited text no. 3
Kauffman CA. Histoplasmosis: A clinical and laboratory update. Clin Microbiol Rev 2007;20:115-32.  Back to cited text no. 4
Cunha VS, Zampese MS, Aquino VR, Cestari TF, Goldani LZ. Mucocutaneous manifestations of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome: Particular aspects in a Latin-American population. Clin Exp Dermatol 2007;32:250-5.  Back to cited text no. 5
Mansoor CA, Bhargavan PV, Rajanish R, Nair LR. Disseminated histoplasmosis. Indian J Orthop 2013;47:639-42.  Back to cited text no. 6
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Correspondence Address:
Mansoor C Abdulla
Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Malappuram - 679 338, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_721_17

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