Abstract
A young, unmarried, immunocompetent female presented with complaints of fever and altered sensorium, along with lesions over the face and trunk. A provisional diagnosis of disseminated herpes simplex with giant molluscum contagiosum was made. However, cutaneous biopsy of the lesions showed numerous cryptococcal organisms which stained positive to periodic acid-Schiff. This case is reported to sensitise physicians to keep cryptococcosis as a differential diagnosis in such types of skin lesions, as the lesions resemble that of molluscum contagiosum very closely.
Case history
A 21-year-old unmarried woman presented with high grade fever, of four days' duration, vomiting, headache, altered sensorium and two episodes of seizures on the day of admission. On the third day of admission, she started to develop multiple flesh-coloured lesions all over her face and trunk. During the period of hospitalization the lesions increased in number and size and involved the oral cavity including the palate (Figure 1).
Multiple flesh coloured lesions covering the face including lips, tongue and palate
She was anaemic and was maintaining vitals. A central nervous system (CNS) examination showed an altered sensorium, bilateral pupils which were normal in size and reaction, her deep tendon reflexes and tone were normal, the plantars were bilateral equivocal and any signs of meningeal irritation were absent. The rest of the general physical and systemic examinations were normal. A possibility of disseminated herpes simplex with giant molluscum contagiosum was considered and she was put on systemic antibiotics, acyclovir and decongestant therapy.
Laboratory reports showed anaemia (haemoglobin 8 g/dL); a cerebrospinal fluid (CSF) examination revealed normal biochemistry with a total cell count of 10 (70% polymorphs, 30% lymphocytes); an acid fast bacilli stain was negative; no organisms were seen on a gram stain and the culture was sterile. The chest radiograph, ultrasound abdomen and a routine urine examination were normal. Blood and urine culture were sterile. Tests on her immunoglobulin M for herpes simplex virus-I were negative; magnetic resonance imaging showed a prominence of the third ventricle suggestive of meningitis; an enzyme-linked immunoadsorbent assay for HIV-1 and -2 was negative. A cutaneous biopsy was done to confirm the diagnosis.
Initially she showed a gradual improvement in sensorium, but later she deteriorated progressively and subsequently died. The cutaneous biopsy showed numerous cryptococcus organisms with minimal inflammatory infiltrates, lesions described as gelatinous and spores of cryptococcus stained positively with periodic acid-Schiff.
Discussion
Cryptococcus neoformans can cause infection in individuals with normal and impaired immune functions, but especially in HIV-infected patients. 1 However, approximately one-third of patients had no known underlying medical conditions. Recently, there has been an increase in the incidence of cryptococcosis even among patients considered immunocompetent. 2 Cryptococcal infection may occur in all age groups. It has been reported that even apparently ‘normal’ patients, i.e. those without identifiable immune system disorders, may have subtle selective lymphocyte deficiencies. 3
The difficulty in the clinical diagnosis of crytococcal infection lies in the paucity and nonspecificity of signs and symptoms, the insidiousness of the course and coexistence with single or multiple infections and/or other diseases. The most common manifestation of disseminated cryptococcosis is infection of the CNS, which produces meningitis or encephalitis. However, a systemic spread can cause almost any organ to become infected. The skin is the most common extraneural site of infection, affecting 10–20% of those with systemic involvement and the majority have disseminated infection. Cutaneous lesions are an ominous sign as they are often the first presenting symptoms of systemic disease. 4 A high index of suspicion is mandatory because cryptococcal skin involvement is non-specific and produces a wide variety of lesions.
Once a diagnosis of cutaneous cryptococcal infection has been made it is imperative to initiate a search for systemic involvement including obtaining a chest X-ray, blood and urine cultures, CSF examination (biochemistry, cytology, India ink stain, cryptococcal antigen and culture) and testing for the presence of the cryptococcal antigen in the serum.
The mainstay of treatment for cryptococcosis is amphotericin B with or without flucytosine. Unfortunately, it is highly toxic, has poor CSF penetration and has a high relapse rate. More recently, the azoles have emerged as alternate therapies in patients who cannot tolerate amphotericin B. Fluconazole has been found to be particularly effective due to its high bioavailability, excellent CSF penetration and long half-life and is now the drug of choice for prophylactic therapy and used as a consolidation therapy after the successful induction with amphotericin B and 5-flucytosine. 5 The mortality of disseminated cryptococcosis is 70–80% in untreated patients compared with 17% treated with systemic anti-fungal agents.
This case of disseminated cryptococcosis is presented in order to highlight the importance of an awareness of such fatal disease and the maintenance of a high index of clinical suspicion even in apparently normal individuals. It is critical to begin with a thorough investigation into any cutaneous lesion in high-risk individuals in order to initiate rapid therapy.