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Full clinical cases submission template

TITLE OF CASE
Corticosteroid induced Crptococcal meningitis in non HIV patient

SUMMARY

Cryptococcus neoformans is the most frequent cause of mycotic meningitis in man.

Cryptococcus affects people of all ages and has a world-wide distribution. It is the
fourth most common infection in AIDS (CD4 counts <100). Cases also occur in patients
with other forms of immunosupression and in apparently immunocompetent
individuals. Chronic high-dose steroid may precipitate such an immunocompromised
state and thus create susceptibility to fungal infections. In our case, we describe a 14
year old male who was on steroids for tubercular meningitis for a period of 8 weeks
after which he developed cryptococcal meningitis. Attention is drawn to the increasing
number of reported cases of this disease which have been associated with
steroid therapy and this possibility should be remembered when investigating patients
with Tubercular meningitis especially if they are being treated with steroids.

BACKGROUND

Cryptococcus neoformans is an opportunistic infection. It is the fourth most

common infection in AIDS (CD4 counts <100) but has also been seen in patients
on prolonged corticosteroids which account for about 1/3 non HIV cases [1]. High
steroid dose can decrease migration and inhibit chemotaxis of neutrophils, inhibit
phagocytosis, intracellular killing and decrease production of proinflammatory
cytokines [2]. We are reporting a case of Cryptococcal Meningitis in a HIV
seronegative 14 year old boy who was being treated on steroids for tubercular
meningitis.

CASE PRESENTATION

A 14 year old male ( weight 39 kgs ) , presented with low grade fever, cough with expectoration and
dizziness since 20 days. There was history of one episode of generalized tonic clonic
seizure. There was no history of anorexia, weight loss or focal neurological deficit. Past
history and family history was non-significant.
On examination, he was conscious, oriented, moderately built and nourished. Patient
was afebrile and hemodynamically stable. Respiratory exam showed decreased air entry
in left lower zone with associated dull percussion note. Patient had terminal neck
rigidity on neurological exam but negative kerning’s sign, however rest of the systemicexamination was normal.

INVESTIGATIONS
On laboratory investigations, complete hemogram, liver function tests, kidney function
tests were within normal range. Sputum for AFB was negative. HIV was negative, CD3
and CD4 count was normal. Chest x ray showed left sided pleural effusion (Figure1).
MRI Brain was normal. A CSF exam was done which revealed no cells,
protein of 159gm%, and sugar of 73mg%. CSF gram stain, culture, AFB
stain, India ink and cryptococcal antigen were negative. Pleural fluid analysis

Revised September 2014 Page 2 of 6

demonstrated total of 80 cells, 80% lymphocytic and 20% neutrophils, protein of
4.7gm%, Sugar of 62mg% and ADA of 4.1 U/L. CSF TB-PCR of the patient came out
to be positive and he was started on anti-tubercular therapy (ATT) category II i.e two months of
intensive phase comprising of isoniazid, rifampicin,ethambutol ,streptomycin and pyrazinamide
followed by continuation phase with isoniazid and rifampicin for seven months thereafter,
steroids
and anti-epileptics. He was discharged after seven days of hospital stay. He again presented to the
emergency room after 35 days of discharge with complaints
of fever, headache and vomiting since 7 days with one fresh episode of seizure along
with sudden onset weakness on right side and altered sensorium. On reviewing the
history it was found that he had discontinued ATT since 15 days but was taking steroids and
antiepileptics .
On neurological examination, he was in altered sensorium with a Glasgow Coma Scale of 9/15.
Power in right half of the
body was 2/5 and right plantar was extensor. Rest of the systemic examination was
unremarkable. A repeat CSF was done which showed no cells, protein 38mg/dl and sugar of
61mg/dl. MRI Brain was suggestive of late sub-acute infarct in left fronto-parietal region
with early hydrocephalus (Figure 2). CSF crptococcal antigen and india ink were negative .
As the patient had been noncompliant , he was resumed on category 2 ATT and kept under
observation. One week later, he had an episode of sudden onset of loss of
consciousness. He regained consciousness after 3-4 hrs. CSF was repeated again which
showed TLC of 20 Cells, 90% lymphocytes, Protein of 274gm/dl, sugar of 70 mg/dl,
CSF Catridge Based Nucleic Acid Amplification test to look for resistance against isoniazid
and rifampicin was negative. However, CSF Cryptococcal antigen by latex
agglutination and India ink came out to be positive this time (Figure 3). LJ Medium culture which
was sent during first admission came out to be positive for Mycobacterium. Tuberculosis and
drug
sensitivity test done by the conventional method sent in the first admission showed resistance to
Isoniazid. MRI brain showed enhancing nodular lesion seen in left frontal region likely
cryptococcoma with areas of restricted diffusion seen in B/L basal ganglia likely due to
ischemic insult ( Figure 4 ).

DIFFERENTIAL DIAGNOSIS

TREATMENT

In the first presentation, patient was given weight calculated category 2 ATT regimen comprising
of isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin. Steroids were initially given
for a week intravenously at a dose of 0.4mg/kg/day in four divided doses.
At the time of discharge, he was shifted to oral dexamethaone at dose of 0.3 mg/kg/day in four
divided doses.
On second admission, patient was noncompliant with anti-tubercular therapy but continued with
steroids. He was restarted on the same regimen as already described along with a tapered dose of
steroid at 0.2 mg/kg intravenously.
A week later, after the CSF came out to be positive for cryptococcal antigen, Deoxycholate
Amphotericin was added and given for a total duration of six weeks followed by Fluconazole as
maintainence. Steroids were tapered gradually and stopped over the next two weeks
Revised September 2014 Page 3 of 6
Also, since the LJ medium showed Mycobacterium Tuberculosis but drug sensitivity to the
primary drugs showed resistance to isoniazid , tab levoflox 500mg once a day was added and the
primary Anti Tubercular drug regimen continued on account of monoresistance not classifying as
Multidrug Resistant Tuberculosis.

OUTCOME AND FOLLOW-UP

The sensorium of the patient showed slight improvement . His Glasgow Coma Scale improved
to 11/15 with spontaneous eye opening and moving the left side of the body . However the power
did not recover on the right side and he continued on Ryles tube feeding . There was no fresh
episode of seizure or focal
neurological deficit.

DISCUSSION
Cryptococcosis is a life-threatening infection caused by two main species, Cryptococcus
neoformans and Cryptococcus gattii.. Meningitis in immunocompetent host is usually attributed
to C.gattii worldwide; although few cases have been caused by C. var grubii [3] Host becomes
vulnerable to cryptococcosis whenever there is defect in T cell
mediated host defense mechanisms [4]. Diagnosis of Cryptococccal meningitis can be
reliably done by Serum cryptococcal latex agglutination titer which has a sensitivity of
87% in HIV-negative while CSF latex agglutination assay is 95% sensitive .India ink
preparation has a sensitivity of 50 % in HIV negative and > 90 % in HIV positive [5].
However, CSF Culture remains the gold standard. Studies have reported cases of
cryptococcal meningitis with prolonged steroid use being given for some other
condition. Goldstein and Rambo (1962) reported eight cases of cryptococcosis whose
onset occurred during or immediately following steroids [6]. It has also been reported
from six patients with Systemic Lupus Erythematosus in the medical literature over the past 10
years. Four of the
six had been treated with steroids for periods ranging from 10 weeks to 6 years [7]. In an Indian
Case Report 13-year-old girl developed cryptococcal meningitis after taking
prednisolone (4.5 mg/kg body weight/day) for a year for autoimmune hemolytic anemia
[8].In our case also, we describe the patient to be on steroids for tubercular meningitis
for a period of 8 weeks after which the cryptococcal antigen was found to be positive in
CSF as well as the organism was seen on India Ink preparation while on
the initial presentation both cryptococcal antigen and india ink were negative. A course of
amphotericin B combined with flucytosine was considered. However, due to nonavailability of
resources an
extended course of amphotericin alone was given followed by maintainence on Fluconazole

LEARNING POINTS/TAKE HOME MESSAGES

1 Immunocompetent individuals may develop cryptococcal meningitis though rarely .

2 When patient continues to show partial response or develop further neurological complications
despite on therapy, possibility of dual infection may be considered .

3 Chronic high-dose steroid may precipitate an immunocompromised state and

thus create susceptibility to fungal infections.

Revised September 2014 Page 4 of 6

REFERENCES
1. Bicanic T, Harrison TS. Cryptococcal meningitis. Br Med Bull. 2004; 72(1) :
991 PubMed -18.

2 Klein NC, GoCHU, Cunha BA. Infections associated with steroid use. Infect Dis
Clin North Am. 2001; 15(2): 423-32.

3. . Meningitis Due to Cryptococcus gattii in an Immunocompetent Patient. Rajesh T Patil, Jyoti

Sangwan, Deepak Juyal, Sumit Lathwal. J Clin Diagn Res. 2013 October; 7(10): 2274–2275.

4. Kontoyiannis DP, Peitsch WK, Reddy BT, Whimbey EE, Han XY, Bodey GP,
Roiston KV. Cryptococcosis in patients with cancer.
Entrez. PubMed. Clin Infect Dis. 2001; 32:145-50.

5. P Satish Chandra, T Mathew, G Gadre, S Nagrathna, A Chandramukhi, A

Mahadevan, SK Shanker. Cryptococcal Meningitis: Clinical, diagnostic and
therapeutic overviews. Neurol India. 2007; 55:226-32 PubMed .

6. Goldstein, E., and O. N. Rambo. Cryptococcal infection following steroid

therapy. Ann. Int. Med. 1962; 56 (1).

7. M Aneees, Sydney Sbrar. Cryptococcal meningitis in steroid treated Systemic

Lupus Erythematosus. Postgrad Med J. 1975 Sep ; 51(599): 660–662.

8. PR Kumari, PR Shahapur, PS Rao. Corticosteroid induced cryptococcal

meningitis. Ind jour of Micro. 2005; 23(3):207 PubMed -208.

FIGURE/VIDEO CAPTIONS
Fig 1: Chest X-ray: left pleural effusion

Fig 2: MRI Brain( at first presentation): s/o late sub-acute infarct in left front - parietal
region with early hydrocephalus

Fig 3:Cryptococcus on India Ink

Fig 4:MRI Brain (after 8 weeks of steroids) : enhancing nodular lesion seen in left
frontal region likely cryptococcoma

Revised September 2014 Page 5 of 6

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