First Subungual Cryptococcosis Described in an HIV Patient with Disseminated Cryptococcosis

• Cutaneous cryptococcosis occurs in 10–15% of patients with disseminated cryptococcosis.

• It presents as papulonodular molluscum-like lesions, but it can also produce a wide variety of lesions.

• Cryptococcal infection of the nail unit has never been reported.

• Diagnosis requires pathology and culture.

• Surgical excision associated with systemic therapy is the best treatment approach in managing subungual cryptococcosis.

Disseminated cryptococcosis is one of the most common life-threatening infections in patients with human immunodeficiency virus-1 (HIV). It is caused by the monomorphic yeast-like fungus, Cryptococcus neoformans [1]. After a primary infection in the lungs, the disease can disseminate via a hematogenous route to various organs, including the central nervous system and skin [2]. Secondary skin lesions are observed in 10–15% of patients with disseminated cryptococcosis [3]. Cutaneous cryptococcosis is nonspecific. It typically presents as papulonodular molluscum-like lesions, but it can also produce a wide variety of lesions including, purpura, pustules, nodules, abscesses, ulcers, acneiform lesions, granulomas, and cellulitis [4]. Nail involvement has never been reported in the course of cutaneous cryptococcosis. Here, we describe a case of subungual cryptococcosis in an HIV patient with disseminated cryptococcosis.

A 28-year-old woman was referred to the dermatology outpatient department to evaluate a subungual swelling of the right middle finger. The patient had a history of HIV with disseminated cryptococcosis involving the central nervous system, lungs, and urinary tract. She had been treated with antiretroviral therapy, amphotericin-B, and fluconazole and had shown complete remission during follow-up. By the time of the consultation, she was undertaking antiretroviral therapy and a maintenance dose of oral fluconazole (150 mg) once a day. Five months before the consultation, the patient started developing a painful growth under the nail that eventually bled and ulcerated, leading to total nail destruction with periungual swelling and inflammation. Dermatological examination of the nails revealed an ulcero-burgeoning nodule of 1 × 1 cm size over the subungual area of the right middle finger with onycholysis, eschar, and erosion (Fig. 1). On general examination, the patient also had multiple skin-colored umbilicated papules of linear arrangement on the limbs, which mimicked molluscum contagiosum. Before the biopsy, our suspected diagnoses regarding the subungual lesion were superficial acral fibromyxoma, amelanotic melanoma, subungual Bowen disease, or subungual squamous cell carcinoma. The X-ray of the right middle digit excluded bone destruction within the nail apparatus. We performed a surgical excision of the subungual lesion. Histopathological analysis demonstrated multiple histiocytic granulomas centered by encapsulated yeast cells that stained with periodic acid Schiff and Grocott, suggesting C. neoformans (Fig. 2). Culture grew Cryptococcus neoformans var. neoformans. After the excisional biopsy, we did not give any further treatment to the patient. After 9 months of follow-up, there was no recurrence of the lesion.

This is the first reported case of cryptococcal infection of the nail unit. Although the patient had disseminated cryptococcosis with skin lesions evocative of cutaneous cryptococcosis, subungual cryptococcosis was not suspected. Definitive diagnosis required pathology and culture. Pathology revealed multiple histiocytic granulomas. This critical response of histiocytes indicates that the patient’s immunity was restored after she received antiretroviral therapy.

The precise pathogenesis of nail involvement in our patient remains speculative. Subungual cryptococcosis may be secondary to the dissemination of the disease via a hematogenous route. It could have originated from the dorsal branches to the palmar digital arteries and the fingertip’s dorsum that supply blood to the nail bed, matrix, and fold.

Due to the lack of data, it is still difficult to define the best management for subungual cryptococcosis. In our patient, the cryptococcal infection of the nail unit was recalcitrant to systemic therapy while the remaining infection cleared. The lesion’s resistance to oral treatment may indicate that systemic antifungal agents alone are not sufficient to cure subungual cryptococcosis. We suggest that surgical excision associated with systemic therapy is the best treatment approach in managing subungual cryptococcosis. In conclusion, subungual cryptococcosis has never been reported; however, recognizing this rare cutaneous manifestation is essential as the number of patients with HIV, particularly vulnerable to cryptococcosis, is still on the rise [5].

The subject has given her written informed consent to publish this case, including publication of images.

The authors have no conflicts of interest to declare.

The authors have no funding sources.

Drafting of the manuscript: Yasmine Slimani. Examination of the nail biopsy: Rajaa Karam and Farida Marnissi. Critical revision of the manuscript for important intellectual content: Soumiya Chiheb and Fouzia Hali.