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Middle-aged Woman With Headache,Middle-aged Woman With Headache,


A 54-year-old Hispanic housewife presents to the emergencydepartment with a 3-week history of moderatelysevere, progressive, generalized, pulsating headache.The headache, which is partially relieved by propoxyphenenapsylate, is associated with weakness, vomiting of recentonset, and intermittent bilateral blurred vision. The symptomsbegan after an incident in which the patient’s sonwas stabbed.


54-year-old Hispanic housewife presents to the emergencydepartment with a 3-week history of moderatelysevere, progressive, generalized, pulsating headache.The headache, which is partially relieved by propoxyphenenapsylate, is associated with weakness, vomiting of recentonset, and intermittent bilateral blurred vision. The symptomsbegan after an incident in which the patient's sonwas stabbed.


The patient reports night sweats but nofever, rigors, or chills. She has lost several pounds becauseof decreased appetite. There is no history of ataxia,seizures, syncope, confusional state, paresthesias, or bladderor bowel dysfunction. The patient denies cough,dyspnea, chest pain, hematemesis, melena, and abdominalpain. She does not use alcohol, tobacco, or illicit drugs.She is in a monogamous relationship with her husband.She has had no blood transfusion or tattoos and has nottraveled outside the United States.


The patient is cachectic and looks ill.The pulse rate is 84 beats/min and regular; respirationrate, 24 breaths/min; blood pressure, 110/70 mm Hg.She is afebrile and well hydrated. Oral thrush is noted.There is no clubbing, cyanosis, adenopathy, rash, or ankleswelling. The thyroid is not palpable; no breast massesare detected. Skull and spine are normal; the carotid arteriesare equal and palpable. The patient is alert and oriented.The cranial nerves are intact and fundi are normal.There is no focal motor or sensory deficit. Deep tendonreflexes are equal bilaterally, and plantar reflexes are flexor.Neck is supple. There are no meningeal or cerebellarsigns. Romberg sign is negative. Other systemic examinationresults are normal.

Laboratory studies.

White blood cell (WBC) count,6500/μL, with neutrophils, 74%; lymphocytes, 20%;monocytes, 6%. Hemoglobin, 11.3 g/dL; platelet count,360,000/μL; erythrocyte sedimentation rate, 70 mm/h.Serum sodium level, 136 mEq/L; potassium, 3.5 mEq/L;chloride, 101 mEq/L; blood urea nitrogen, 14 mg/dL;serum creatinine, 0.8 mg/dL; blood glucose, 107 mg/dL.A CT scan of the head is normal. A lumbar punctureshows increased opening pressure; WBCs, 39/μL, all lymphocytes;glucose level, 42 mg/dL; and protein level,70 mg/dL.The laboratory technician summons you quicklyto look at an India ink-stained smear of the cerebrospinalfluid (CSF).

What does the slide suggest is wrong--and to whatdiagnosis does the clinical picture point?


Tuberculous meningitis


Pneumococcal meningitis


Listerial meningitis


Viral meningitis


Cryptococcal meningitis


Cryptococcosis (also called torulosis or Europeanblastomycosis) is an acute, subacute, or chronic systemicinfection caused by a round or oval yeastlike fungus,



Cryptococcal infection, which occursworldwide, became much more widespread with theAIDS epidemic. In the developed world, the incidence ofcryptococcal meningitis in patients with AIDS is 5% to 10%.The incidence of invasive

C neoformans

in the UnitedStates has declined by 30% to 50% since 1996, whenHAART--which included widespread use of proteaseinhibitors--was introduced to treat HIV infection.


There are more than 20 species of cryptococci,but

C neoformans

is the only one that causes infectionin humans. It reproduces by narrow-based budding.The organism is found in soil and decayed wood chips,especially if these have been contaminated with pigeondroppings.Initial infection occurs through inhalation of the fungus;this is followed by colonization of airways, which canresult in pneumonia or dissemination to the skin ormeninges in immunocompromised persons.

Risk factors.

Although immunosuppression is amajor predisposing factor, up to 50% of patients with cryptococcalinfection have no apparent risk factors. Patientswith immunologic defects in T-cell-mediated host defensemechanisms appear to be at increased risk for progressivecryptococcosis. In addition to AIDS, other important riskfactors include organ transplantation, chemotherapy, prolongedcorticosteroid use, lymphoreticular malignancies(especially Hodgkin disease), and sarcoidosis.


CNS disease.

The onset of CNS cryptococcosismay be acute or insidious. Acute manifestations are morecommon in patients with AIDS; the most frequent ismeningoencephalitis.The clinical presentation may be mild and nonspecific.Symptoms range from headache, nausea, irritability,somnolence, clumsiness, depression, agitation, and confusionwith a decline in cognitive function to frank obtundation.The cranial nerves may be involved, and the patientmay notice decreased visual acuity, diplopia, and facialnumbness or weakness. Seizures usually occur late in thecourse of the illness.Physical examination results may include fever andabnormal neurologic findings, such as cranial nervepalsies, motor or sensory deficit, cerebellar dysfunction,hyperreflexia, and papilledema. A CT scan or MRI may revealhydrocephalus with cerebral edema. CSF abnormalitiesinclude higher opening pressure with elevated proteinand low glucose levels and lymphocytic pleocytosis.In patients with CNS cryptococcosis, an India inkstain of a CSF smear reveals the organism and culture ispositive for

C neoformans.

Bear in mind, however, thatas many as 20% of patients with a positive culture do nothave a clearly abnormal CSF profile. In patients withmeningitis, cryptococcal antigen is usually detected inthe CSF.

Pulmonary disease.

Pulmonary cryptococcosis maybe asymptomatic and self-limited; however, in patientswith AIDS it can cause severe progressive pneumoniawith respiratory failure. A patient may complain of coughwith expectoration, fever, malaise, shortness of breath,and pleuritic chest pain. The chest radiograph typicallyshows diffuse infiltrate and consolidation with hilar or mediastinaladenopathy.

Other organ involvement.

Cryptococcosis may involveseveral sites. Single or multiple skin lesions arefound in 5% to 10% of patients. Lesions on the face or scalpmay appear as small papules, pustules, erythematous induratedplaques, soft subcutaneous masses, draining sinustracts, or large ulcers with undermined edges. Regionallymphadenopathy is occasionally present.Osteocytic bony lesions, cold abscesses, and joint involvementsometimes occur. Pyelonephritis, prostatic cryptococcosis,endophthalmitis, and adrenal gland involvementhave been reported rarely in disseminated disease.


A high index of suspicion is essential in immunocompromisedpatients, especially those with AIDS who presentwith neurologic, pulmonary, or cutaneous manifestations.The diagnosis may be confirmed by several methods:

  • Demonstration of encapsulated budding yeasts in smearsof body fluids, exudates, or other specimens. The organismsmay be identified by India ink staining or positivemucicarmine, Gomori, methenamine, or Masson-Fontanastaining. Histopathologic examination of various tissuebiopsy specimens may also be used in identification.
  • Detection of cryptococcal polysaccharide antigen inserum or CSF has a sensitivity and specificity of morethan 95%.
  • Positive culture of CSF, blood, or urine specimens.


CNS cryptococcosis.

The recommended regimenfor patients with AIDS and cryptococcal meningitis isIV amphotericin B, 0.7 mg/kg/d with oral flucytosine,25 mg/kg qid, for 2 weeks initially, followed by oralfluconazole, 400 mg/d, for 8 weeks, and 200 mg/dthereafter.Until 2001, US Public Health Service guidelines hadrecommended maintenance therapy with fluconazole forlife. The agency now advises that secondary prophylaxiscan be discontinued if the patient has completed a courseof initial therapy, remains asymptomatic, and has a sustained(that is, more than 6 months) increase in CD4count to more than 100/μL to 200/μL following HAART.For AIDS patients whose CD4 count is less than100/μL, the recommended primary prophylaxis is oralfluconazole, 200 mg, 3 times a week.For patients who do not have AIDS, oral fluconazoleand flucytosine have been used, especially in those withno impairment of mental status, CSF antigen titers of lessthan 1:128, negative blood culture, and negative CSF Indiaink smear.

Pulmonary or cutaneous cryptococcosis.

No specificguidelines are available for treatment of pulmonaryor cutaneous cryptococcosis. Close observation is sufficientif the disease is mild, localized, and stable and CSFfindings are normal. Fluconazole has been used in moresevere cases.


At discharge, the patient's headache had completelyresolved, but she was lost to follow-up.



  • Dolin R, Masur H, Saag M, eds. Cryptococcosis. In: AIDS Therapy. 2nd ed.New York: Churchill Livingstone; 2003:498-510.
  • Mandell GL, Bennett JE, Dolin R, eds. Cryptococcus neoformans. In: Mandell,Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed. Philadelphia:Churchill Livingstone; 2000:2707-2718.
  • Meyohas MC, Roux P, Bollens D, et al. Pulmonary cryptococcosis. Clin InfectDis. 1995;21:628-633.
  • Murakawa GJ, Kerschmann R, Berger T. Cutaneous Cryptococcus infection andAIDS. Report of 12 cases and review of the literature. Arch Dermatol. 1996;132:545-548.
  • Powderly WG. Cryptococcal meningitis and AIDS. Clin Infect Dis. 1993;17:837-842.
  • Saag MS, Powderly WG, Cloud GA, et al. Comparison of amphotericin B withfluconazole in the treatment of acute AIDS-associated cryptococcal meningitis.N Engl J Med. 1992;326:83-89.
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