Acquired immunodeficiency syndrome manifested as disseminated cryptococcosis

The Journal

of Emergency

Medane,

Vol 3. pp 275-279.

1985

Prmted r the USA

l

1985 Pergamon

CopyrIght

Press ilc

ACQUIRED IMMUNODEFICIENCY SYNDROME MANtFESTED AS DlSSEMtNATED CRYPTOCOCCOStS Gordon Pittard,* ‘Senior

Dwrsron

MD,

and Donna Seger,?

FACEP

Resdent.

Department of Emergency Medrcrne, Unrversrty Hospital of Jacksonville, Flonda. tResrdency Education Dtrector. Department of Emergency Medrcrne. Unwersity Hospttal of Jacksonville, Flortda, and Assrstant Professor. of Emergency Medrctne Department of Surgery, Unrversrty of Florida College of Medrcrne Reprmt address: Donna Seger, MD. Department of Emergency Medrcrne. Unlversrty of Jacksonville, 655 West 8th Street, Jacksonville, FL 32209

0 Abstract-A 32-year-old male homosexual presented to the eme%mcy department (ED) with the ciinieal picture of a lwlspicifii ihess. While in the ED, he experienced a first-time seizure. thmtpwd tomography 0) showed an enhancing mass iesion. Antibacterial therapy was stafied and contim& until a second Lumbar puncture (LPI, 36 hours after admission, showed disthct yeast forms. Subsequent institution of appropriate therapy dii not prevent the pat&& death. The cause of death was disseminated cryptococcosis secondary to acquired immunodeficiency syndrome (AIDS). Cl Keywords-AIDS; cryptococcosis; first seizure; Kaposi’s sarcoma

Introduction Acquired immunodeficiency syndrome is characterized by recurrent episodes of opportunistic infections in previously healthy individuals. Its presentations are varied and often subtle. Patient survival beyond an acute infection may depend on early institution of aggressive therapy. We present a case of AIDS manifested by disseminated cryptococcosis, cytomegalovirus (CMV) colitis, and Kaposi’s sarcoma. RECEIVED:

MD,

2 May 1985; ACCEPTED:

caseReport A 32-year-old white male was brought to our hospital by prison officials. He had complained of headache, nausea, vomiting, diarrhea, loss of appetite, and weight loss of 8 Ibs over a five-day period. A 20 lb weight loss had been noted over the preceding 6 months. No exposure to hepatitis or tuberculosis was reported, and he denied homosexual activity. The patient was taking no medications at the time of presentation. His past medical history was negative. The patient was alert and cooperative and appeared chronically ill, but was in no acute distress. Initial physical examination revealed a blood pressure of 120/56 mm Hg, pulse of 64 beats per minute, respirations of 16, and an oral temperature of 101.4”F. Sclerae were nonicteric; HEENT was within normal limits; neck was supple; lungs were clear. Cardiovascular examination revealed a regular rhythm without any murmurs. Diminished bowel sounds were heard in the abdomen, which was soft to palpation with diffuse tenderness. Rectal examination revealed loose sphincter tone with yellow, guaiac-negative stool. A 2-cm erythematous lesion was observed on the

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Pittard and Donna

Seger

left shoulder and a similar lesion on the left A repeat LP 36 hours after admission forearm. No peripheral lymphadenopathy produced an opening pressure of 23.7 cm was noted. The results of a neurological CSF. Analysis revealed 9 white blood cells, examination were normal. 89% lymphocytes, and 11% PMNs. Many During examination the patient became yeastlike organisms were also seen. An Inunresponsive. He was moved to a resuscita- dia ink preparation showed encapsulated tion area where he was observed to have a yeast suggestive of Cryptococcus. At that pulse of 64 beats per minute, a blood pres- time, antibacterials were discontinued, and sure of 150/70 mm Hg, and unlabored res- a regimen of amphotericin B and 5-flucypirations of 24. He experienced a short gen- tosine was started. eralized seizure followed by a brief postictal During the patient’s hospital course, biperiod. Further questioning indicated that opsies of the upper extremity skin lesions the patient had suffered from hepatitis of were obtained and were consistent with unknown type in 1976. The patient also ad- Kaposi’s sarcoma. Bone marrow biopsy mitted to homosexual contacts on numerous showed mild hypercellularity with no maoccasions in the past, but denied homosexlignant sites or granuloma. Flexible sigmoidoscopy was performed because of persistual contacts within the preceding 16 months. ent diarrhea. Biopsy specimens and cultures Intravenous drug abuse was denied. Laboratory results included normal se- of the bowel revealed acute colitis with cytomegalovirus infection. Serum testing durrum electrolytes, a BUN of 11 mg/dL, creatinine of 1.0 mg/dL, and glucose of ing his hospitalization showed no elevation 122 mg/dL. White blood cell count was of liver enzymes. Hepatitis A antibody (IgG) was positive. Erythrocyte sedimenta5,400/mm3 with a hemoglobin of 9.9 g/dL, hematocrit of 29.7070, and a differential of tion rate was 86. VDRL and RPR were 55 neutrophils (polymorphonuclear neutrononreactive. Urine, sputum, and blood culphilic, PMNs), 33 bands, and 6 lymphotures were negative. No ova or parasites cytes. Amylase was 60 IU (nL 44 to 128). were found in stool cultures. Arterial blood gases showed a pH of 7.49, After institution of antifungal therapy, Pal 73, and a pC0, of 32 with a F,O, of the patient’s condition seemed to improve. He had no respiratory complaints, and re21%. A chest roentgenogram was within peat blood gases showed a PO, in the 90s. normal limits. An ECG revealed a normal sinus rhythm. Computed tomography (CT) On the fifth day after admission, the paof the brain with contrast medium demontient was found unresponsive in his hospital resuscitation was strated an enhancing lesion in the right room. Cardiopulmonary frontal region (Fig 1). No shift of midline instituted and appropriate pharmacologic structures was seen. The lesion was con- therapy was administered. However, the pasidered to be consistent with an abscess or tient’s cardiac rhythm could not be restored. neoplasm. Despite an apparent intracerebral Autopsy revealed splenomegaly and dismass, lumbar puncture (LP) was deemed seminated cryptococcosis. Budding yeast necessary. A small amount of clear cerebro- was found in the brain, meninges, lungs, spinal fluid (CSF) was removed with an spleen, and liver. Final diagnoses were acsyndrome, disopening pressure of 46 cm CSF. Analysis quired immunodeficiency showed 13 white blood cells and 3 red blood seminated cryptococcosis, cytomegalovirus cells with 20070lymphocytes and 8O@Jo PMNs. colitis, and Kaposi’s sarcoma. CSF protein was 111 mg/dL and glucose was 46 mg/dL. Gram’s stain revealed no Discussion bacteria, but suggested budding yeast. The admitting physicians chose to institute broad The association of Pneumocystis carinii spectrum antibacterial antibiotics after ap- pneumonia (PCP), Kaposi’s sarcoma, and propriate cultures were obtained. male homosexuality was reported during

277

AIDS Manifested as Disseminated Cryptococcosls

Flgun

1. CT ewn with contrast

showtng

an enhandng

the summer of 198 1.1-4 Once the syndrome of AIDS was defined, retrospective diagnoses of AIDS were made dating at least to 1979. The Centers for Disease Control defines AIDS as a disease at least moderately indicative of underlying cellular immunodeficiency (specifically, including Kaposi’s sarcoma, PCP, or other opportunistic infections) in the absence of known causes of immunodeficiency. Infections that have been associated with AIDS are listed in the Table.6 Groups at risk for the syndrome include male homosexuals, intravenous drug abusers, Haitians, hemophiliacs and other blood product recipients, infants of highrisk parents, and sexual consorts of affected patients. 7-9 Our patient presented with a history and clinical status strongly suggesting the syndrome; his death secondary to overwhelming opportunistic infection confirmed it. Cryptococcosis is frequently encountered in the patient with AIDS. Cell-mediated immunity (CMI), which is dramatically impaired in AIDS, is necessary for adequate

leaion In rfght frontal

T8ble 1. InfectIons

Asmckted

region.

with AIDS’

Protozoai CIyptosporidiiis Pneumocystis carinii pneumonia Strongyioidosis Toxoplasmosis Fungal Aspergillosis Candidiasis Coccidioidomycosis Cryptococcosis Histoplasmosis Bacterial Atypical mycobacteriosis Nocardiosis Viral Cytomegalovirus Herpes simplex virus Progressive multifocal kukoencephektpathy

defense against the Cryptococcusorganism. Athymic mice and patients with Hodgkin’s and other lymphoreticular diseases have diminished CM1 and are also susceptible to this fungal infection. Most cases of cryptococcosis involve only mild or asymptomatic pulmonary disease. The rare case

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Gordon

of blood-borne extrapulmonary cryptococcal dissemination typically presents as acute or chronic meningitis. Headache is the most frequent presenting complaint. Other presentations include ocular manifestations, ataxia, nausea, meningismus, cranial nerve palsies, and seizures. Altered mental status may reflect developing hydrocephalus, and focal neurologic deficits may result from the intracerebral cryptococcomas.Lo”’ Cryptococcal meningitis classically produces CSF lymphocytic pleocytosis (less than 500 cells). CSF may also reveal hypoglycorrhachia, which is more commonly seen in CNS tuberculosis or coccidioidomycosis. Opening pressure is elevated in 90% of cases. If polysaccharide-encapsulated cryptococcal organisms are visible against the dark background of India ink, the diagnosis can be easily made. However, India ink smears are positive in only 50% of cases. For rapid diagnosis, the procedure of choice is demonstration of capsular antigen in CSF by latex agglutination. This test is positive in 90% of cryptococcal meningoencephalitis. The vast amount of newly emerging literature on AIDS documents numerous cases of cryptococcal meningitis.12-‘4 The crucial factor in determining patient survival has been early institution of aggressive therapy. Results of therapy in AIDS patients have been uniformly discouraging. The 50% to 70% cure seen in noncompromised hosts treated with amphotericin B (alone or in combination with S-flucytosine) has not been reported in AIDS victims.” Factors

Pittard and Donna Seger

that are poor prognostic indicators in nonAIDS patients include high titer CSF cryptococcal antigen, positive India ink smear with less that 20 white blood cells per cubic millimeters of CSF, hypoglycorrhachia, elevated opening pressure on LP, and preexistent immunocompromise (malignancy, steroid therapy). Whether or not these factors affect the already poor prognosis in the AIDS patients has yet to be determined.16 Our case demonstrates the importance of suspecting opportunistic infections (including cryptococcosis) in patients at risk for AIDS. The finding of an enhancing cerebral mass lesion on CT scan in a setting consistent with AIDS specifically suggests toxoplasmosis, cryptococcosis,” or CNS lymphoma. I8 While the patient’s prognosis was extremely poor from the outset, it was not improved by delay in diagnosis, or by institution of ineffective therapy. Many infections associated with AIDS, such as disseminated mycobacterium avium intracellulare, cytomegalovirus, and cryptosporidiosis, cannot be effectively treated at this time. However, others including PCP, herpes simplex virus, cryptococcosis, and toxoplasmosis often respond to appropriate therapy. Pending development of treatment aimed at correcting the immunosuppression, potential therapeutic successes may come from early diagnosis of opportunistic infection and institution of appropriate therapy.

Acknowledgement-Thanks to Julia Meeks for help in preparation of the manuscript.

REFERENCES I. Masur H. Michelis MA, Greene JB, et al: An outbreakof community-acquired pneumocystis carinii pneumonia. NEnglJMed 1981; 305:1431-1438. 2. Gottlieb MS, Schroff R, Schanker HM, et al: Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a newly acquired cellular immunodeficiency. N Engl J Med 1981; 305:1425-1431. 3. Centers for Disease Control: Pneumocystis pneumonia - Los Angeles. MMWR 198 I ; 30:250-252. 4. Centers for Disease Control: Kaposi’s sarcoma and pneumocystis pneumonia among homosexual men

5.

6. 7.

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-New York City and California. MMWR 1981; 30:305-308. Jaffe HW, Bregman DJ, Selik RM: Acquired immune deficiency syndrome in the United States: the Rrst 1000cases. J/n/err Dis 1983; 148:339-345. Seger DL: Acquired immune deficiency syndrome. J Emer Med 1984; 2:117-128. Fauci AS, Macher AM, Longo DL, et al: Acquired immunodeficiency syndrome: epidemiologic, clinical immunologic and therapeutic considerations. Ann lnfern Med 1984; 100:92-106. Lederman M, Ratnoff OD, Scillian JJ, et al: Im-

AIDS Manifested

as Dlssemlnated

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Cryptococcosls

paired call-mediated immunity in patients with classic hemophilia. N Engl J A&f 1983; 308:79-83. 9. Small, CB, Klein RS, Friedland GH. et al: Community-acquired opportunistic infections and defective cellular immunity in heterosexual drug abusers and homosexual men. Am J Med 1983; 74:433-441. 10. Youmans GP, Paterson PY: The Biologic and Clinical Basis of Infectious Diseases. New York, WB Saunders, 1975. 11. Hoeprich PD: Infectious Diseases: A Modern Treatise oJInfectious Processes, 2nd ed. Hagerstown, Harper & Row, 1977. 12. Mildvan D, Mathur U, Enlow RW, et al: Opportunistic infections and immune deficiency in homosexual men. Ann intern Med 1982; %:700-704. 13. Vandepitte J, Verwilgher R, Zachee P: AIDS and cryptococcosis (Zaire, 1977) [letter]. Lancer 1983

(Apr);925-936. 14. Aledort LM: AIDS: An update. Hasp Pratt 198.1 (Sept):159-171. IS. Bennett JE: A comparison of amphoteracin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979;

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80:176.

17. Pitchenik AE, Fischl MA, Walls KW: Evaluation of cerebral mass lesions in acquired immunodeficiency syndrome (letter). N Engl J Med 1983; 308: 1099.

18. Snider WD, Simpson DM, Aronyk KE, et al: Prtmary lymphoma of the nervous system associated with acquired immunodeficiency syndrome. h’ Engl

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