Skin-nontumor / Clinical Dermatology - Histoplasma capsulatum

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Skin-nontumor / Clinical Dermatology

Infectious disorders

Fungi - Histoplasma capsulatum

Reviewer: Ha Kirsten Do, M.D., IUPUI (see Reviewers page)
Revised: 21 November 2010, last major update September 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition
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● Infection is caused by inhalation of airborne spores of Histoplasma capsulatum, a dimorphic saprophytic fungus found in soil contaminated with bird or bat feces

Epidemiology
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● Highest incidence is in North America, particularly in the central states along the Mississippi River basin
● Histoplasma is endemic to Southeast US (80% of this population may have positive intradermal histoplasmin skin test), Mexico, Africa, Asia
● Transmission of disease is by inhalation of spores that can be found in feces of bats, starlings (type of bird) and chickens; causes a primary pulmonary pneumonia

Clinical features
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There are several clinical manifestations of histoplasmosis:
● Acute pulmonary histoplasmosis: almost 90% patients have no symptoms
● Chronic pulmonary histoplasmosis: occurs mostly in patients with underlying lung disease
● Progressive disseminated histoplasmosis: occurs mostly in immunosuppressed patients
● Ocular histoplasmosis syndrome: eye disease, occurs in 1-10% of the patients
● Cutaneous histoplasmosis: erythema nodosum or erythema multiforme

● Pneumonia is self-limited in immunocompetent patients, but disseminates in immunocompromised (very young, very old, HIV+) to liver, spleen, bone marrow, nodes, lung, rarely to skin
● Disseminated disease: strongly associated with AIDS; patients have fever, weight loss, splenomegaly; variable cutaneous lesions
● Cutaneous lesions are nodules, papules, ulcers; less commonly macules, pustules or vesicles

Diagnosis
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● Culture shows tan-white-brown wooly mold at 25-30 C on Sabouraud dextrose agar
● Organisms have delicate, septate hyphae, 1-2 microns thick, with large rough-walled macroconidia 5-15 microns
● Reverts to yeast at 37 C on sheep blood agar
● Yeast is 2-4 microns, budding, single nuclei, round/oval with thin rigid walls

Treatment
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● Most with minimal disease require no treatment
● Moderate to severe cases require antifungal drugs, usually Itraconazole x 9 months in immunocompetent patients, Itraconzazole followed by IV amphotericin B in immunosuppressed patients

Case reports
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● 5 year old healthy child with atypical variant causing disseminated cutaneous disease (Rev Inst Med trop S Paulo;1999:41:195)
● 27 year old woman with multiple cutaneous lesions (Arch Pathol Lab Med 2004;128:e15)
● 33 year old HIV+ man with recurrent disseminated disease (Arch Pathol Lab Med 2001;125:571)

Clinical images
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Diffuse erythematous maculae with central necrosis in disseminated histoplasmosis

Micro description
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● Isolated intracellular organisms and large aggregates surrounded by chronic inflammatory cells and fibroblasts (but no neutrophils or eosinophils); also epithelioid granulomas with variable caseation
● May be narrow based budding of spores

Micro images
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Figure 1: multiple budding yeasts in deep dermis (arrow indicates yeast); 2: GMS stain; 3/4: lacto-phenol cotton blue stain of mold shows characteristic thick-walled tuberculate macroconidia and microconidia (arrow indicates macroconidia)

Figure 1: 2-3 mm hyperpigmented papules; 2: dermal basophilic spherules 2-4 microns

Granulomatous infiltrate

Slide culture with small microconidia and tuberculate macroconidia

Within macrophages

Positive stains
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● PAS, GMS, Giemsa

Molecular / cytogenetics
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● PCR probes are now available
● Best diagnostic test is the urinary ELISA

Differential diagnosis
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● Aspergillosis
● Blastomycosis
● Carcinoid lung tumors
● Chlamydial pneumonia
● Coccidioidomycosis
● Legionella pneumonia
● Lymphoma
● Mycoplasma pneumonia
● Pancoast tumor (tumors at extreme apex of either lung in the superior sulcus)
● Pneumocystis carinii
● Pneumonia - bacterial, fungal or viral
● Sarcoidosis
● Tuberculosis

Additional references
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● University of Adelaide, Centers for Disease Control

End of Skin-nontumor / Clinical Dermatology > Infectious disorders > Fungi - Histoplasma capsulatum

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