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Disseminated histoplasmosis mimicking secondary syphilis

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Disseminated histoplasmosis mimicking secondary syphilis
Tony A Pastor MD1, Maura J Holcomb MD1, Kiran Motaparthi MD1, Sarah J Grekin MD2, Sylvia Hsu MD1
Dermatology Online Journal 17 (11): 10

1. Department of Dermatology
2. Department of Pathology
Baylor College of Medicine, Houston, Texas


A 34-year-old, HIV-positive man living in Texas presented with a 2-week history of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face, and extremities, including the palms. Initially secondary syphilis was suspected. However, RPR was negative. Histopathologic examination revealed a lymphocytic infiltrate with numerous intra-histiocytic fungal organisms. GMS and PAS stains were positive, consistent with the diagnosis of histoplasmosis. We report a case of disseminated histoplasmosis clinically mimicking secondary syphilis.


Histoplasma capsulatum is a dimorphic, saprophytic, soil-based fungus that is endemic throughout the Ohio and Mississippi river valleys. Inhalation of the organism can lead to a self-limiting flu-like illness in immunocompetent hosts. Cases of disseminated disease affecting the liver, spleen, bone marrow, lymphoreticular system, and gastrointestinal tract are seen in immunocompromised individuals, particularly in HIV patients with CD4 counts less than 200. Skin manifestations of histoplasmosis are rare, with 11 percent of reported cases having skin involvement [1]. The following patient represents a case of disseminated histoplasmosis with cutaneous lesions mimicking those of secondary syphilis.

Case report

Figure 1Figure 2
Figure 1. Violaceous papules on the shoulder

Figure 2. Violaceous papules on the forehead

Figure 3Figure 4
Figure 3. Hyperpigmented macules on the palms

Figure 4. Split papules in the oral commissures and confluent ulcers with white exudate on the distal tongue

A 34-year-old HIV-positive man living in Texas presented with a 2-week history of fever, malaise, and myalgias. These were subsequently followed by the development of painful lesions on his tongue and papules over his chest, face, and extremities. His past medical history was significant for hepatitis C and untreated HIV, both of which were diagnosed 6 months prior to presentation. On physical examination, the patient had multiple violaceous papules on the trunk (Figure 1), face, including the forehead (Figure 2), periocular and perioral areas, and all four extremities (Figure 3). There were also hyperpigmented macules on the palms and split papules on the oral commissures. On the distal tongue there were confluent ulcers with white exudate (Figure 4). Based on morphology, the differential diagnosis included secondary syphilis, deep fungal infection, and lichen planus. Hepatomegaly was noted on percussion, with the liver spanning 20 cm at the midclavicular line. Non-tender cervical lymphadenopathy was noted as well. Abnormal laboratory values included a CD4 count of 22, HIV viral load of 27,700 copies/ml, normocytic anemia with hemoglobin of 8.2, elevated creatinine of 2.2, and elevated ferritin of 1543 ng/ml. RPR was negative despite several dilutions performed to rule out the prozone phenomenon. Serology for treponemal-specific antibodies (MHA-TP) was also negative. Evaluation of the buffy coat smear of peripheral blood, serology for Cryptococcus, and fungal smears of blood and bone marrow also failed to yield a diagnosis.

Figure 5
Figure 5. Nodular lymphohistiocytic infiltrates with intracellular organisms 2-4 microns in diameter, stained with PAS

A punch biopsy from the left arm revealed nodular infiltrates of lymphocytes and histiocytes in the dermis, along with numerous intra-histiocytic organisms approximately 2-4 microns in diameter, which stained positively with PAS (Figure 5). Based on clinical-pathologic correlation, the diagnosis of disseminated histoplasmosis was made. Later, an elevated urine histoplasmosis antigen test (18.7) and fungal cultures of bone marrow and blood provided additional diagnostic confirmation. The patient was treated with liposomal amphotericin B 250 mg IV daily for 14 days and then transitioned to oral itraconazole 200 mg po BID for 1 month. Follow-up 1 month after treatment demonstrated resolution of skin lesions. The patient was subsequently started on HAART.


Histoplasma capsulatum was discovered in 1905 by Samuel Darling [2]. Today, histoplasmosis plays a significant role as an opportunistic infection, affecting more than 10 percent of HIV patients living in endemic areas [3]. The infection is acquired by inhalation of conidia and mycelia fragments found in nitrogen-rich soil. Two variants have been described as clinically important causes of disseminated histoplasmosis. The first is Histoplasma capsulatum var. duboisii, which is endemic in the African subcontinent and most commonly produces cutaneous and osseous lesions. Histoplasma capsulatum var. capsulatum is found mostly in North and South America and more commonly presents with pulmonary infections [4]. Infected immunocompromised patients present with a wide variety of clinical manifestations, including meningitis, adrenal insufficiency, hepatosplenomegaly, lung infiltrates, bone marrow infiltration, and mucocutaneous findings [5].

Although not the most common presentation, cutaneous involvement is described in 11 percent of cases of disseminated histoplasmosis [1]. A wide variety of clinical lesions have been reported, including erythema multiforme-like, herpetic, molluscum contagiousum-like, acneiform, exfoliative, and vasculitic [6]. Some of the more unique cutaneous lesions in infected patients have been described as pyoderma gangrenosum-like lesions, diffuse ulcerations, and verrucous plaques [7, 8]. The majority of cases featuring cutaneous involvement describe papules, plaques, nodules, or ulcers with the most commonly affected areas being the face, chest, and upper extremities [9].

Our patient also presented with lingual ulcerations with abundant exudate. The most common physical finding in patients with chronic progressive disseminated histoplasmosis is an oropharyngeal ulcer found in up to 50 percent of cases. These ulcers are commonly found on the tongue, buccal mucosa, larynx, gums, and lips. Ulcerations tend to be deep, indurated, and painless – similar to those found in syphilis [2]. Oral histoplasmotic lesions can vary and have been described in the literature as ulcerative, nodular, plaque-like, and vegetative, but can resemble any granulomatous disease [10].

The efficacy of itraconazole monotherapy in the treatment of disseminated histoplasmosis with cutaneous lesions has been demonstrated in numerous cases, with resolution of skin lesions within several weeks and without relapse [11]. In the case presented, initial treatment with amphotericin B was selected because of the severity of the condition.

Secondary syphilis was originally suspected in this patient because of the morphology of the cutaneous lesions and the palmoplantar involvement. Split papules and oral ulcers have also been described in secondary syphilis [12]. To our knowledge, this is the first reported case of cutaneous histoplasmosis mimicking secondary syphilis.


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