Sayuri Yuge1, Ivander Bastazini Júnior1, Maria Carolina Melo Coelho1 and Cleverson Teixeira Soares2
Departments of 1Dermatology and 2Pathology, Lauro de Souza Lima, Institute, Rodovia Cte, João Ribeiro de Barros km 225/226, Bairro Aimorés, Bauru, São Paulo, Brazil. E-mail: firstname.lastname@example.org
Accepted September 5, 2005.
Cryptococcosis is an opportunistic infection that usually affects immunocompromised hosts (1). It is caused by the opportunistic yeast Cryptococcus neoformans, which is present in the environment worldwide (e.g. pigeon droppings, vegetables, soil) (1, 2). Four serotypes have been identified: A (var. rubii), D (var. neoformans) and B, C (var. gatii) (2, 3). We present a case of an immunocompetent patient with cutaneous cryptococcosis without clinical or laboratory evidence of dissemination.
A 75-year-old housewife, from an urban area of Brazil, presented with a 7-month history of a non-tender plaque on her right forearm. She received antibiotics for presumed bacterial cellulites without improvement. The patient was otherwise healthy. She denied any history of previous relevant trauma, although she reported daily exposure to soil and wood debris (gardening) and also easy disruption of sun-exposed areas of skin after minor trauma.
Examination revealed erythematous, smooth and firm plaque on her right forearm, size 15 × 4 cm (Fig. 1). Sun-exposed skin showed solar elastosis, Bateman’s purpura and stellate scars particularly of the dorsal forearms and hands. There was no lymphadenopathy. Her entire physical examination was unremarkable. A biopsy specimen from the lesion showed dermal infiltrate organized in a granulomatous pattern. Numerous rounded bodies surrounded by a refractile gelatinous capsule were found scattered throughout the involved skin. Yeast cells stained with mucicarmine, periodic acid-Schiff and methanamine-silver (Fig. 2). Skin culture grew C. neoformans. Complete blood count, biochemical panel, immunoglobulins, CD4/CD8 cell counts and chest radiograph were normal. Culture and antigen latex agglutination test of blood and urine were negative. Lumbar puncture was unnecessary because the patient was without clinical or laboratory findings to suggest dissemination. Human immunodeficiency virus (HIV), hepatitis B and C serologies were negative. She was treated with fluconazole 400 mg/day for 3 months with minimal improvement. After a 3-month cycle of amphotericin B 50 mg 3 times a week (total dose: 2250 mg) healing was obtained. Nevertheless, amphotericin B was discontinued as signs of renal injury were detected. Subsequently itraconazole 200 mg/day for 6 months was given and clinical remission was achieved.
Fig. 2. Skin biopsy showing extensive dermal infiltration with predominance of vacuolar histiocytes. Hematoxylin-eosin stain, original magnification ×40 (a). Cryptococcus showing a radiated aspect. Periodic acid Schiff stain, original magnification ×400 (b).
Fig. 1. Cutaneous cryptococcosis. Large erythematous plaque with poorly defined borders on right forearm (a). Close-up of elbow (b).
A clinical diagnosis of cutaneous cryptococcosis is difficult to make due to lack of pathognomonic skin lesion (2, 3). It can simulate bacterial cellulitis (4, 5), discoid lupus erythematosus (6), molluscum contagiosum (7), herpes (8) and other diseases. Although the most described lesions are nodule, ulcer and whitlow (2, 3).
Cutaneous cryptococcosis is mostly attributed to inhalation of Cryptococcus spores and later haematogenous dissemination (i.e. secondary cutaneous cryptococcosis), nevertheless some authors suggest the possibility of cutaneous inoculation (i.e. primary cutaneous cryptococcosis (PCC)) (1–4). In our patient the portal of entry was not defined and a lung infection that spontaneously cleared cannot be ruled out.
The existence of PCC is still controversial (2) and some authors consider it a “sentinel” of cryptococcal systemic infection (4). PCC is defined in the literature by identification of C. neoformans in the skin lesion and presence of a chancriform syndrome, without evidence of systemic dissemination (2, 4). However, just a few authors could demonstrate the chancriform syndrome (5), most of them described patients with isolated cutaneous lesion without systemic involvement (6, 7).
The French Cryptococcosis Study Group (2) proposed some additional criteria to distinguish PCC from secondary cutaneous cryptococcosis. They found that PCC occurred frequently in patients from rural area, with solitary skin lesion or lesions confined to a limited body area, particularly on unclothed areas (limbs) and without signs of extracutaneous disease. Furthermore, prior history of trauma, pre-existing skin lesion at the same body site or exposure to pigeon droppings, soil and wood debris are further evidences of PCC. We detected in our patient most of the criteria described above, such as lesions confined to unclothed areas, possible skin injury (activities predisposing to wounds and fragile skin of dorsal forearms), exposure to possible contaminated source (soil and dust), absence of systemic signs or antigen detection and favourable outcome. Association between serotype D of C. neoformans and skin lesions has been reported (2), although in our case we could not identify the Cryptococcus serotype due to technical limitations.
The treatment of choice for cryptococcosis depends on the anatomical site of involvement and the host’s immune status. The guidelines published by the Infectious Disease Society of America recommended fluconazole 200–400 mg/day for 3–6 months for cutaneous involvement in immunocompetent hosts, nevertheless there are no detailed studies of therapeutic effectiveness. Itraconazole and amphotericin B are acceptable alternatives for patients with more severe disease (9).
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