Non‐healing ulcer in a farmer

A 70-year-old paddy field farmer presented with a large painful ulcer over the right forearm of 7 months duration, which initially started as a small papule that ruptured to form a progressively enlarging ulcer. He denied any previous trauma, fever, or cough. There was no history of travel, animal contact, or any relevant family history. Earlier, he was treated with oral steroids and antibiotics without much success. Examination revealed a 15 × 4 cm ulcer on the right extensor forearm with verrucous crusting and an erythematous border, with mild tenderness and minimal local rise in temperature. A second ulcer was present on the flexor aspect with yellowish slough and sloping margins. (Figure 1a-c). There was no regional lymphadenopathy, and sensations were intact. Wedge incisional biopsy from a representative area revealed a focally ulcerated epidermis with neutrophilic exocytosis and irregular acanthosis. The underlying dermis showed ill-formed granulomas with Langhans, as well as foreign body giant cells. There were clusters of multinucleated cells and singly scattered pleomorphic round to oval pale staining yeast cells with thin walls and perinuclear halos along with focal areas of necrosis (Figure 2). The peri-adnexal dermis showed lymphoplasmacytic and neutrophilic infiltrate and extravasation of red blood cells. PAS, GMS, and Mucicarmine stains were also done (Figure 3a-b). Fungal culture showed no growth. HIV 1, 2 antibodies, HCV, and HbsAg were negative. The CD4/CD8 ratio was also within normal limits. c. Cryptococcosis (Cryptococcus neoformans infection). The serum cryptococcal antigen was positive. Because of the COVID pandemic, the patient was lost to follow-up, and phone calls to him at the given number were unattended. We could not investigate further with a cerebrospinal fluid (CSF) study, urine antigen titers, and CT of the chest and abdomen to exclude disseminated infection. Cryptococcus neoformans is a ubiquitous encapsulated yeast found in decaying wood, soil, vegetable matter, and bird feces. It causes cryptococcosis, an opportunistic infection. It usually affects immunocompromised hosts (individuals with HIV, malignancy, organ transplant recipients, and those on corticosteroid therapy).1 The entry route is the respiratory system by inhalation of airborne fungal conidia and hyphal fragments.2 Skin lesions tend to be secondary to dissemination, although primary cutaneous lesions are well documented.3 A diagnosis of primary cutaneous cryptococcosis (PCC) requires the presence of C. neoformans on the biopsy specimen and the exclusion of visceral involvement, which is often difficult as skin lesions can sometimes be the only manifestation of visceral disease and also can be the forerunners of disseminated disease by 2–8 months.4, 5 A 2003 review on PCC proposed clinical diagnostic criteria for PCC, including a skin lesion that is confined to a limited body area or present at a solitary site or a whitlow-like lesion in an unclothed area (limbs), with possible regional lymphadenopathy and a history of prior injury with a hobby or occupation predisposing to skin injury, exposure to potentially contaminated sources like avian excreta, wood debris, soil or needle contaminated with C. neoformans, living in a rural area, no underlying disease predisposing to cryptococcosis, no systemic signs, no extracutaneous sites positive for C. neoformans, a negative antigen detection, D serotype of C. neoformans and a favorable outcome of infection.6 Cutaneous lesions can sometimes be an early marker or the only symptom, even in a disseminated disease. An antigen positivity may not always indicate dissemination, as severe local infections can also show antigen positivity. However, it is essential because it can indicate impending cryptococcal meningitis early.6 Cutaneous lesions observed in PCC include umbilicated papules, vesicles, pustules, plaques, nodules, purpura, ulcers, acneiform lesions, granulomas, cellulitis, draining sinuses, and a whitlow.7, 8 Fever or systemic symptoms are often absent. Cellulitis or soft tissue abscess-like presentation mimicking a bacterial infection is seen in immunocompromised patients.2 Differing morphology reflects on a dynamic host immune system trying to eliminate the infectious agent for years together.7 The gold standard for diagnosis is culture and histopathology.5 Histopathological features mentioned in the literature include circumscribed granulomas, compactly arranged histiocytes, multinucleate giant cells (both Langhans and foreign body), numerous intracytoplasmic yeasts (phagocytosed), central necrosis, fibrotic nodules, and ellipsoid, oval, or spherical cells with clear zones or halo that represent unstained capsule.9 Histopathology does not help to differentiate between a primary and secondary lesion.9 Routine hematoxylin and eosin will not stain Crytpococcus, and special stains like Grocott methenamine silver, periodic acid-Schiff, and Alcian blue are required.10 Treatment varies depending on the immunocompetence of the host, the number of sites involved, and CNS involvement. For the immunocompromised, in renal failure, and for higher fungal burden, liposomal amphotericin B 3–4 mg/kg/day IV along with flucytosine (100–125 mg/kg/day) induction therapy for 2 weeks followed by fluconazole 400 mg consolidation phase for 6–12 months is used. In the immunocompetent, 0.7–1 mg/kg of Amphotericin B will suffice.11 Current practice is to use Itraconazole at 100–400 mg/day doses for 3–6 months instead of fluconazole.5 Prognosis is usually good for the immunocompetent host; however, there is a single case report of a patient with an untreated cutaneous lesion on the toe for 5 months, which progressed to systemic dissemination.5 Immunocompromised hosts are vulnerable to cryptococcal meningitis and pneumonia.2 In conclusion, though cryptococcosis is amenable to antifungal therapy, prognosis is often guarded in immunocompromised patients and depends on their comorbidities, underlying immunosuppression, and the extent of the lesions.