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Case Reports and Small Case Series
February 1999

Eyelid Nodule: A Sentinel Lesion of Disseminated Cryptococcosis in a Patient With Acquired Immunodeficiency Syndrome

Arch Ophthalmol. 1999;117(2):268-269. doi:

Cutaneous cryptococcosis is a rare infection caused by Cryptococcus neoformans an encapsulated saprophytic yeast. It is 4 to 8 µm in diameter and is surrounded by a polysaccharide capsule that lives especially well in dust and soil contaminated by the excreta of pigeons.1 The initial site of infection is usually the lung, where cryptococcosis occurs without symptoms and persists in a latent stage for a long time.2 Hematogenous dissemination of the yeast may involve any organ of the body, principally the brain (70%-90% of the cases) with a meningoencephalitis or a subacute meningitis and, to a lesser extent, the skeleton, eyes, and skin.2 We describe a man affected by acquired immunodeficiency syndrome in whom disseminated infection with C neoformans started with a nodule on the border of his right eye.

Report of a Case.

A 37-year-old man with acquired immunodeficiency syndrome had a 3-week history of a papular lesion on the border of the right side of his upper eyelid (Figure 1). The clinical suspicion was of either a molluscum contagiosum or a neoplasm derived from the meibomian glands. The lesion was surgically removed. The patient's immunologic test results were as follows: total leukocyte count, 5 ×109/L; CD4+ cells, 0.019 ×109/L; CD8+ cells, 0.039 ×109/L; and the CD4+/CD8+ ratio, 0.05 (normal ratio, 1-2). The patient was taking antiretroviral therapy with indinavir (800 mg, 3 times daily), stavudine (40 mg, 2 times daily), and lamivudine (150 mg, 2 times daily).

Figure 1. 
Small papular lesion on the border of the right eyelid.

Small papular lesion on the border of the right eyelid.

Histopathologic examination showed numerous cryptococcal organisms with large polysaccharide capsules, surrounded by a granulomatous inflammation inside the superficial and mid dermis (Figure 2). Cryptococcal antigen was detectable in serum (titer 1:8192) and cerebrospinal fluid (titer 1:512). A chest x-ray film showed interstitial thickening, but a bone scan, a computed tomographic scan of the cranium, and an ophthalmoscopic examination showed no abnormalities. Therapy with amphotericin B, 1 mg/kg per day, and flucytosine, 150 mg/kg per day, was started but after 15 days additional multiple dome-shaped, flesh-colored, umbilicated papules, and ulcerated nodules appeared on the face, arms, and the dorsal aspect of the hands. The complete clinical remission lasted 5 weeks after therapy.

Figure 2. 
Numerous cryptococci organisms surrounded by gelatinous capsules (periodic acid–Schiff, original magnification ×1000).

Numerous cryptococci organisms surrounded by gelatinous capsules (periodic acid–Schiff, original magnification ×1000).


Human cryptococcal disease is a potentially fatal infection that develops mainly in predisposed individuals with defective cell-mediated immunity.1,3 Since the advent of acquired immunodeficiency syndrome, cryptococcosis has become more frequent, involving from 5% to 10% of patients during their life, 10% to 15% of whom had cutaneous involvement.4 Most prominent on the face and neck, less frequently located on the trunk and extremities, the typical clinical cutaneous manifestations are umbelicated papules with a tiny, central hemorrhagic crust quite similar to molluscum contagiosum.1 Less often, violaceous papules, vesicles in a varicelliform pattern, crusted plaques, subcutaneous nodules, or cellulitis have been reported.4 The most frequent ophthalmic manifestations of infection with C neoformans involve the posterior segment of the eye with papilledema, optic nerve atrophy, endophthalmitis, and choroiditis.5 One existing report describes limbal and choroidal mass and another iris inflammatory mass in patients with acquired immunodeficiency syndrome.6,7

The prognosis depends on the degree of the patient's immunodepression, the involvement of C neoformans, and the prompt start of therapy.3,4 The patient we observed is interesting because he showed a single nondiagnostic lesion on the upper border of the eyelid as a sentinel lesion that preceded the spreading of the cryptococcal infection by 5 weeks. A rapid diagnosis permitted the prompt start of appropriate therapy. Notwithstanding this, our patient experienced an initial spread of cryptococcal lesions on his skin although then serum and the colony-stimulating factors titer of cryptococcal antigens were decreasing slowly. Now, after a 22-month follow-up, the patient is well. Occasional relapses of the opportunistic infection have been controlled with amphotericin B.

Corresponding author: Donato Calista, MD, San Patrignano Medical Center, San Patrignano, 47037 Rimini, Italy (e-mail: bufalini@cessn.unibo.it).

Murakawa  GJKershmann  RBerger  T Cutaneous cryptococcus infection and AIDS: report of 12 cases and review of the literature.  Arch Dermatol. 1996;132545- 548Google ScholarCrossref
Wai  FNKa  TL Cutaneous cryptococosis-primary versus secondary disease: report of two cases and review of literature.  Am J Dermatopathol. 1993;15372- 377Google ScholarCrossref
Sarosi  GASiberfarb  PMTosh  FE Cutaneous cryptococcosis: a sentinel of disseminated disease.  Arch Dermatol. 1971;1041- 3Google ScholarCrossref
Calista  DStagno  ALandi  C Cutaneous lesions of disseminated cryptococcosis as the initial presentation of advanced HIV infection.  J Eur Acad Dermatol. 1997;8140- 144Google ScholarCrossref
Kestelyn  PTaelman  HBogaerts  J  et al.  Ophthalmic manifestations of infection with Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome.  Am J Ophthalmol. 1993;116721- 727Google Scholar
Muccioli  CBelfort Junior  RNeves  RRao  N Limbal and choroidal Cryptococcus infection in the acquired immunodeficiency syndrome.  Am J Ophthalmol. 1995;120539- 540Google Scholar
Charles  NCBoxrud  CASmall  EA Cryptococcosis of the anterior segment in acquired immunodeficiency syndrome.  Ophthalmology. 1992;99813- 816Google ScholarCrossref