Skin Lesions of Disseminated Histoplasmosis Resembling Kaposi’s Sarcoma

Akira Kawashima AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan

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Haruka Uemura AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan

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Shinichi Oka AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan

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A 29-year-old man with newly diagnosed HIV infection and a 6-week history of recurrent fever, weight loss, and rashes was referred to our hospital. He had immigrated to Japan from Brazil 15 years previously. Physical examination revealed a body temperature of 40.2°C and generalized erythema with partial crusting on his face, trunk, and limbs (Figure 1A). Laboratory tests showed a white blood cell count of 3.54 × 109 cells/L, CD4 count of 21 cells/μL, hemoglobin of 9.5 g/dL, aspartate aminotransferase of 133 U/L, alanine aminotransferase of 108 U/L, lactate dehydrogenase of 948 U/L, serum creatinine of 0.69 mg/dL, and β-d-glucan level of 164.8 pg/mL. A polymerase chain reaction (PCR) test for human herpes virus 8 (HHV-8) was negative. Ophthalmic examination revealed iris nodules, papillary edema, and hard white exudates (Figure 1B). Positron emission tomography scan showed fluorine-18 deoxyglucose accumulation in multiple subcutaneous nodules and the spleen, bone marrow, and bones (Figure 2).

Figure 1.
Figure 1.

(A) Generalized erythema with partial crusting was noted on the patient’s face, trunk, and limbs. The lesions resembled Kaposi’s sarcoma. (B) An ophthalmic examination performed 2 weeks after admission revealed iris nodules (red arrow), papillary edema (yellow arrow), and hard white exudates (white arrows).

Citation: The American Journal of Tropical Medicine and Hygiene 108, 3; 10.4269/ajtmh.22-0459

Figure 2.
Figure 2.

Positron emission tomography scan showing fluorine-18 deoxyglucose accumulation in multiple subcutaneous nodules, the spleen, bone marrow, and bones throughout the body.

Citation: The American Journal of Tropical Medicine and Hygiene 108, 3; 10.4269/ajtmh.22-0459

Although the skin lesions resembled those of Kaposi’s sarcoma, which are not usually biopsied per our protocol, the fever, positive β-d-glucan result, and negative HHV-8 result led us to suspect systemic mycosis. Skin biopsy and bone marrow aspiration were performed, and the specimens were stained with Grocott methenamine silver (Figure 3). The patient was diagnosed with disseminated histoplasmosis (DH) on the basis of PCR and cultures obtained from the skin and bone biopsy specimens.

Figure 3.
Figure 3.

A skin biopsy was performed, and the specimens were stained with Grocott methenamine silver stain (magnification ×400).

Citation: The American Journal of Tropical Medicine and Hygiene 108, 3; 10.4269/ajtmh.22-0459

Histoplasmosis is caused by Histoplasma capsulatum, which is endemic in North, Central, and South America, but not in Japan. As seen in this case, H. capsulatum can remain dormant in the body for over 10 years.1 The patient’s country of origin increased our suspicion for this disease. Disseminated histoplasmosis is an opportunistic infection affecting immunocompromised persons, such as those with HIV.2 It is a progressive extrapulmonary infection that undergoes hematogenous dissemination to the bone marrow, liver, spleen, and lymph nodes,2 and common cutaneous manifestations include papules and oral erosions.3

The treatment of HIV-positive DH involves liposomal amphotericin B for at least 2 weeks or until clinical improvement.2 Antifungal drugs are immediately followed by anti-retroviral therapy (ART).2 Iritis and optic neuritis have been reported in autopsies,4 and blindness due to immune reconstitution inflammatory syndrome (IRIS) was reported.5 Therefore, our patient was treated with liposomal amphotericin B (3 mg/kg) for 4 weeks without ART until the cutaneous and ocular symptoms improved. Two weeks after ART initiation with coformulated bictegravir, emtricitabine, and tenofovir alafenamide, the patient showed no signs of IRIS; therefore, his antifungal treatment was switched to itraconazole (200 mg twice daily). One year after discharge, he had not experienced a relapse.

ACKNOWLEDGMENTS

We are grateful to Masahiro Abe and Minoru Nagi of the Department of Fungal Infection at the National Institute of Infectious Diseases in Japan for performing microbiological tests to identify the fungus.

REFERENCES

  • 1.

    Desmet P , Vogelaers D , Afschrift M , 2004. Progressive disseminated histoplasmosis 10 years after return out of Africa in an immunocompetent host. Acta Clin Belg 59: 274278.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Kaplan JE , Benson C , Holmes KK , Brooks JT , Pau A , Masur H ; Centers for Disease Control and Prevention (CDC) ; National Institutes of Health ; HIV Medicine Association of the Infectious Diseases Society of America , 2009. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58: 1207.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Cunha VS , Zampese MS , Aquino VR , Cestari TF , Goldani LZ , 2007. Mucocutaneous manifestations of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome: particular aspects in a Latin-American population. Clin Exp Dermatol 32: 250255.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Font RL , Parsons MA , Keener MJ , Shaver RP , Foos RY , 1995. Involvement of anterior chamber angle structures in disseminated histoplasmosis: report of three cases. Ger J Ophthalmol 4: 107115.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Ala-Kauhaluoma M , Aho I , Ristola M , Karma A , 2010. Involvement of intraocular structures in disseminated histoplasmosis. Acta Ophthalmol 88: 493496.

Author Notes

Address correspondence to Haruka Uemura, AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku ku, Tokyo, Japan. E-mail: huemura@acc.ncgm.go.jp

Authors’ address: Akira Kawashima, Haruka Uemura, and Shinichi Oka, AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan, E-mails: akawashima@hosp.ncgm.go.jp, huemura@acc.ncgm.go.jp, and oka@acc.ncgm.go.jp.

  • Figure 1.

    (A) Generalized erythema with partial crusting was noted on the patient’s face, trunk, and limbs. The lesions resembled Kaposi’s sarcoma. (B) An ophthalmic examination performed 2 weeks after admission revealed iris nodules (red arrow), papillary edema (yellow arrow), and hard white exudates (white arrows).

  • Figure 2.

    Positron emission tomography scan showing fluorine-18 deoxyglucose accumulation in multiple subcutaneous nodules, the spleen, bone marrow, and bones throughout the body.

  • Figure 3.

    A skin biopsy was performed, and the specimens were stained with Grocott methenamine silver stain (magnification ×400).

  • 1.

    Desmet P , Vogelaers D , Afschrift M , 2004. Progressive disseminated histoplasmosis 10 years after return out of Africa in an immunocompetent host. Acta Clin Belg 59: 274278.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Kaplan JE , Benson C , Holmes KK , Brooks JT , Pau A , Masur H ; Centers for Disease Control and Prevention (CDC) ; National Institutes of Health ; HIV Medicine Association of the Infectious Diseases Society of America , 2009. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58: 1207.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Cunha VS , Zampese MS , Aquino VR , Cestari TF , Goldani LZ , 2007. Mucocutaneous manifestations of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome: particular aspects in a Latin-American population. Clin Exp Dermatol 32: 250255.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Font RL , Parsons MA , Keener MJ , Shaver RP , Foos RY , 1995. Involvement of anterior chamber angle structures in disseminated histoplasmosis: report of three cases. Ger J Ophthalmol 4: 107115.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Ala-Kauhaluoma M , Aho I , Ristola M , Karma A , 2010. Involvement of intraocular structures in disseminated histoplasmosis. Acta Ophthalmol 88: 493496.

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