What is Responsible for This Cauliflower-Like Lesion?

A 36-year-old female with advanced AIDS presented to our HIV clinic with a 2-month history of new facial skin lesions. The patient is not currently on antiretroviral therapy. 

Physical examination. There were 2 approximately 2 cm, tender nodular lesions with crusting and central ulceration on the forehead (Figure 1). The lesions were initially vesicular and painless, but gradually ulcerated and were currently described as painful and pruritic. There were no similar lesions on other parts of the body. 

The patient reported no dyspnea, cough, weight loss, fever, or chills.  

Laboratory tests. The superficial crust from facial lesion was submitted for histologic examination after it dislodged from her forehead. Histologically, there were large numbers of yeast-like organism within the hemorrhagic serum crust admixed with keratin and a dense infiltrate of neutrophils and lymphocytes (Figures 2 and 3). 

(Answre and discussion on next page)

Answer: Cutaneous Cryptococcosis in a patient with advanced AIDS

History

A 36-year-old female with advanced AIDS presented to the HIV clinic with a 2-month history of new facial skin lesions. The patient is not currently onantiretroviral therapy. There were 2 approximately 2 cm, tender nodular lesions with crusting and central ulceration on the forehead. The lesions were initially vesicular and painless, but gradually because ulcerated and were currently described as painful and pruritic. There were no similar lesions on other parts of the body. The patient reported no dyspnea, cough, weight loss, fever, or chills. 

The superficial crust from facial lesion was submitted for histologic examination after it dislodged from her forehead. Histologically, there were large numbers of yeast-like organism within the hemorrhagic serum crust admixed with keratin and a dense infiltrate of neutrophils and lymphocytes.  

Diagnosis

A presumptive diagnosis of cutaneous cryptococcosis was made as the serum cryptococcal antigen was positive at atiter of 1:256. A CD4 cell count at the time was 46 cells/mm3. Although the patient denied any symptoms that indicated central nervous system involvement, she was admitted for a lumbar puncture to rule out meningoencephalitis. Cerebrospinal fluid analysis showed white blood count of 1, red blood count of  6, glucoselevels at 48 mg/dL, protein at 33, and negative cryptococcal antigen and fungal culture. 

A biopsy of the skin lesion stained with periodic acid Schiff stain (PAS) and Alcianblue showed encapsulated yeast organisms typical for cryptococcus. Diagnosis was confirmed after Cryptococcus neoformans grew in culture of the skin lesion. Blood cultures remained negative. 

Discussion

Cryptococcosis is an AIDS defining illness that affects individuals with CD4 counts less than 100cells/mm3.1 There are over 30 species of the Cryptoccocus genus, but the 2 species responsible for causing the majority of human disease are Cryptococcus neoformans and gattii. This opportunistic infection affects the centralnervous system primarily, but can also involve the lungs and skin. Occasionally, the fungus causes hepatitis, osteomyelitis, endophthalmitis, prostatitis myocarditis, and arthritis.2 

Untreated disseminated disease is associated with 100% mortality. In a literature review, cutaneous cryptococcus was a sign of disseminated disease in 6% of the cases and its presence preceded more serious systemic manifestations.3 

Presentation

Disseminated cutaneous cryptococcus has various presentations. Many different lesions have been described but none of these are pathognomonic as these lesions are insidious in growth and become polymorphic with time. They commonly present on the head and neck as painless papules or pustules that have a gelatinous texture that can ulcerate and develop a central hemorrhagic crust.2,4 These lesions may resemble molluscum contagiosum due to the appearance of umbilication but differ as they are flesh-colored with a pearly consistency. 

Other presentations include acneiform papules or pustules, firm or eczematous plaques with or without warts, palpable purpura resembling vasculitic lesions or nodules with hemorrhage resembling bruises.2,4 

Differential Diagnosis

Clinicians should be aware that cutaneous manifestations of cryptococcus may be the presenting sign of disseminated disease in AIDS patients. Differential diagnosis includes molluscum contagiosum, verrucous herpes simplex, cutaneous cytomegalovirus, human papillomavirus nongenital warts, Kaposi’s sarcoma, mucocutaneous leishmaniasis, mycobacterial skin infections, histoplasmosis, and varicella. A complete history, physical examination, and confirmation through histology, culture, and serology are needed to make a diagnosis. 

Treatment

Initiation of antiretroviral therapy was postponed as it can result in immune reconstitution inflammatory syndrome, which is common with cryptococcus in AIDS patients.5,6 Our patient was treated with fluconazole for induction and consolidation therapy and thereafter, with maintenance therapy. 

References: 

1.     Powderly WG. Cryptococcal meningitis and AIDS. Clin Infect Dis. 1993;17(5):837-842.

2.     Negroni R. Cryptococcosis. Clin Dermatol. 2012;30(6):599-609. 

3.     Murakawa GJ, Kerschmann R, Berger T. Cutaneous Cryptococcus infection and AIDS. Report of 12 cases and review of the literature. Arch Dermatol. 1996;132(5):545-548. 

4.     Rook A, Woods B. Cutaneous cryptococcosis. Br J Dermatol. 1962;74(2):43-49. 

5.     Skiest DJ, Hester LJ, Hardy RD. Cryptococcal immune reconstitution inflammatory syndrome: report of four cases in three patients and review of the literature. J Infect. 2005;51(5):e289-297.

6.     Haddow LJ, Colebunders R, Meintjes G, et al. Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. Lancet Infect Dis. 2010;10(11):791-802.