CRYPTOCOCCAL MENINGITIS ASSOCIATED WITH LYMPHADENOPATHY
IN A HIV INFECTED PERSON - A CASE REPORT
Introduction: The incidence of cryptococcal infection is high in developing countries such as India. It is one of the AIDS defining illnesses. The outcome of the disease can be severe unless the disease is diagnosed early in the course of illness.
Case: A 35 year old female patient was admitted to infectious disease department with complaints of severe headache, vomiting, neck pain, blurred vision, fever and body pains. Patient was diagnosed HIV positive eight months ago. Category 1 ATT drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) were given as empirical therapy for suspected tubercular meningitis. On day two CSF report analysis showed presence of Cryptococcus species. By FNAC report tubercular lymphadenopathy was diagnosed. I.V Amphotericin B 30 mg and oral Fluconazole 1200 mg OD were started for treatment of Cryptococcal meningitis along with category 1 ATT. Patient developed hepatotoxicity which was attributed to high dose Fluconazole by naranjo causality assessment scale. Various drug interactions were also noticed.
Discussion and conclusion: The patient diagnosed with cryptococcal meningitis was treated promptly according to the standard treatment guidelines. The patients' drug therapy was assessed and various problems identified were solved. The prompt diagnosis and treatment helped in the successful treatment of the disease.
Cryptococcus neoformans, a type of yeast found worldwide; can cause pulmonary and central nervous system (CNS) infections that can potentially spread to other areas of the body. This infection is called cryptococcosis. HIV/AIDS patients are especially vulnerable to developing the infection. Cryptococcosis is an infection of the central nervous system mainly caused by Cryptococcus neoformans. The fungus is acquired by inhalation and causes the initial lesion in the lungs, though the pulmonary stage of infection is usually asymptomatic. The fungus disseminates in debilitated patients, usually involving the meninges. The disease has been known to mankind since 1890's. Its incidence remained stable till the mid-twentieth century. Ever since the epidemic of HIV in the early 1980's, its incidence has increased among patients of acquired immunodeficiency syndrome (AIDS). Cryptococcosis is one of the most common infections in AIDS and disseminated cryptococcosis occurs in about one-third of AIDS patients. (1,2) About 10% of AIDS patients develop cryptococcal meningitis as their first AIDS defining disease. (3, 4) The clinical picture of CNS involvement ranges from the indolent to classical signs and symptoms of meningitis. In most of the patients the CNS involvement is indicated by headache, fever, mental changes and focal deficits. (5)
Recent data indicates that the incidence of cryptococcal infection is high in developing countries such as India. (6, 7) A few reports of cryptococcosis associated with HIV are available in India. The incidence of cryptococcosis among the HIV infected in India is not known. (8)
In June 2013 A 35 year old female patient was admitted to infectious disease department with complaints of severe headache, vomiting, neck pain, blurred vision, fever and body pains. On general examination, the patient was found to be having mild pallor, swollen cervical lymph nodes and was having neck stiffness. The patient was diagnosed as HIV positive eight months back at the same hospital and patient's husband was also diagnosed as HIV positive. Patient was not on antiretroviral therapy and there was no prior history of tuberculosis or meningitis. There was no familial history of tuberculosis. Almost all laboratory parameters such as hemoglobin, total WBC count etc were within the normal range.
Chest X-Ray, CSF analysis and CD4 count were done. Chest X Ray showed patchy consolidation of right middle lobe and CD4 counts were 361 cells. Sputum sample for AFB staining was collected and FNAC of cervical lymph nodes were also carried out. As an empirical therapy category 1 antitubercular therapy (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) for suspected tubercular meningitis was started. On day two of admission, CSF analysis report came where Indian ink stain was positive and budding encapsulated yeast were seen showing the presence of Cryptococcus species. Sputum AFB test turned out negative and by FNAC report tubercular lymphadenopathy was confirmed. Along with category 1 ATT, i.v Amphotericin B 30 mg and oral Fluconazole 1200 mg OD were started for treatment of Cryptococcal meningitis.
On 9th day of admission patients hepatic function worsened (SGPT 173.2 IU/ml), this was suspected to be caused by high dose of Fluconazole and therefore Fluconazole was stopped. Fluconazole was resumed two days later at a reduced dose of 400 mg OD.
On 12th day of admission, lumbar puncture and CSF analysis were done and in CSF analysis few encapsulated yeasts were seen. The patient was discharged after 14 days as the course of iv Amphotericin was over and patient was stable. The patient was given Fluconazole 400 mg OD for 8 weeks and further low dose 150 mg OD as prophylaxis. Category 1 ATT was also continued.
In this case the prognosis of cryptococcosis was good unlike other reported cases; this can be attributed to the early diagnosis of disease and early start of appropriate drugs. Early diagnosis was possible due to the fact that there has been an increase in incidence of cryptococcal meningitis in HIV patients coming to our hospital. The mortality rate is high for cryptococcosis in immunocompromised patients owing to delay in diagnosis and inability to administer the drug (especially in sub Saharan regions where there are no adequate facilities to administer intrathecal or intravenous Amphotericin and unavailability of Amphotericin ).9
Current practice of anti-cryptococcal therapy in India for immunocompromised patients is Amphotericin B (0.7-1 mg/kg per day) alone or in combination with flucytosine (100 mg/kg per day in four divided doses). Amphotericin B can be administered alone for six to ten weeks or in conjunction with flucytosine for two weeks, followed by Fluconazole for a minimum of ten weeks 10. Flucytosine is not routinely used in India because of its unavailability and high cost.
Hepatotoxicity due to Fluconazole was the only adverse drug reaction noticed during the therapy. This ADR found to be a probable one using naranjo causality assessment scale. Since a large number of drugs were given to the patient, many drug interactions were found. A major severity drug interaction was found between Dexamethasone and Levofloxacin which increases the chances of tendonitis or tendon rupture. Due to this interaction, the clinical pharmacist suggested to change into another antibiotic. 11 Most drug interactions were of moderate or minor severity and were managed with monitoring liver function, electrolyte levels etc. Amphotericin B interacts with corticosteroids resulting in Hypokalemia, since both drugs were essential in this patient the problem was managed by supplementing potassium.
A new protocol for treatment of cryptococcal meningitis was developed in the hospital based on the experience learned from this case and other similar cases in the hospital. Fluconazole dose was reduced and potassium supplementation was included in the protocol as Amphotericin administration usually leads to Hypokalemia. Liver function tests were to be carried on specific dates of treatment for early detection of hepatotoxicity due to Fluconazole.
From the case reported we suggest that immunocompromised patients coming with headache, neck stiffness etc must be promptly investigated for cryptococcal meningitis as early diagnosis still offers the best chance for successful treatment.
In this patient cryptococcal meningitis was the first AIDS defining illness. The prompt diagnosis and evidence based treatment of cryptococcal meningitis helped the patient recover fully. This case shows that prompt diagnosis can help in successful treatment of an otherwise high mortality rate infection.
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