In April 2015, a 42-year-old married male visited the outpatient clinic suffering from high-grade fever and a large painful ulcer around the anus for the past 3 weeks.
Medical history revealed that he was seropositive and diagnosed with HIV in 1997. His history also confirmed high-risk behavior involving anal sexual intercourse with another man. Treatment was deferred repeatedly for antiretroviral treatment (ART) in 1997 and 2005 as his absolute CD4 counts were >400 cells/mm3. For the past 3 months, (2015), he was experiencing low-grade fever with rising temperature in the evening often associated with chills. He suffered from loss of appetite and had lost 15 kg weight in the past 4 months. He has no history of headache, vomiting, cough, breathlessness, and diarrhea.
Clinical Examination revealed oral candidiasis, a large ulcer measuring 8" X 2" around the anus that was painful and bled on touch as shown in Figure 1. There was no lymphadenopathy. Systemic examination was normal. As the ulcer was painful and bled on touch, a skin biopsy and Tzanck Smear test were recommended.
Four days later, on his 2nd visit, as per NACO, his HIV-1 status was confirmed by HIV-enzyme-linked immunosorbent assay. His CD4 count (Absolute count and Percentage) was 10 cells/mm3, CD4-<4%, and plasma viral load was 43,803 copies/ml. Genotypic drug resistance (DR) testing for HIV-1 was done to rule out (r/o) transmitted DR (TDR) or primary DR.
Hemogram, blood sugar level, renal and liver function tests, urine tests were otherwise normal except thrombocytosis. For investigating fever, the following tests were done which were all negative: Malaria antigen test for Plasmodium vivax and Plasmodium falciparum, Dengue NS1, IgM, IgG, HBsAg, hepatitis C virus, venereal diseases research laboratory/Treponema pallidum Hemagglutination, and Herpes IgM, IgG. Blood culture for aerobic and anaerobic organisms showed no growth. All the tests related to fever were insignificant. Koch's infection was also ruled out. He tested IgG positive for toxoplasmosis. He received chemoprophylaxis for opportunistic infections, (Co-trimoxazole, INH, and Azithromycin) and ART regimen of Tenofovir disoproxil fumarate (TDF) + Emtricitabine (FTC) + Efavirenz (EFA) (TDF + FTC + EFV) fixed-dose combination while awaiting the results of DR, and skin biopsy.
There was no improvement in his symptoms despite treatment for over 3 weeks. Thereafter, he was admitted to the hospital with high-grade fever and large painful perianal ulcer. He received intravenous antibiotics along with ongoing medications.
His perianal biopsy report was suggestive of superficial aphthous ulcer. Tzanck smear test was done suspecting herpetic infection but was negative. 18F-fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (18FDG-PET) scan was done which did not show any abnormal uptake suggestive of malignancy. Thus, tuberculosis and malignancy were ruled out by the TB specialist and oncologist. The dermatologist treated the ulcer as a giant herpetic ulcer with valaciclovir 1 g thrice a day for 2 days, thereafter 500 mg thrice a day while continuing the chemoprophylaxis. While on valaciclovir, the ulcer size reduced in size and developed scarring and pigmentary changes.
While this treatment was ongoing, the ART DR report showed he was resistant to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-NRTIs (NNRTIs) while being susceptible to protease inhibitors and integrase strand transfer inhibitors. Before switching the patients' regimen, CD4 and viral load tests were repeated which showed that his CD4 absolute count was 10 cells/mm3 and CD4- below 4% and plasma viral load was 52,935 copies/ml. The regimen selected post DR test report and counseling was Lopinavir/ritonavir (LPV/r) + Lamivudine (3TC) + Raltegravir (RAL). The patient was afebrile and asymptomatic. The skin lesion healed and he was discharged within 15 days while maintaining the ART regimen.
Five days later, while on the new ART regimen, the patient complained of giddiness and loss of balance. The patient was managed conservatively with oral betahistine (Vertin) by an Otorhinolaryngologist. Subsequently, within few days, the symptoms worsened with him developing headache, vomiting, and blurring of vision. Neurological evaluation revealed tendency to fall on either side during tandem walking, bilateral finger nose ataxia, and Romberg's sign was present. Magnetic Resonance Imaging brain suggested acute demyelination with a differential diagnosis of lymphoma.
FDG-PET scan was repeated after a gap of 40 days from the previous scan. It showed a single space-occupying lesion in the vermis of cerebellar area with no other abnormality as shown in Figure 2. Stereotactic biopsy suggested lymphoma- Non-Hodgkin's diffuse large B-cell lymphoma. Immunohistochemistry showed positive expression for CD20 and negative expression for CD-10. Cultures of CSF and tissue did not reveal any aerobic or anaerobic infection. Fungal culture, TB-MGIT, and identification of MAC and Gene Xpert for MTB were negative. EBV was present.
The patient was eventually diagnosed with PCNSL through a process of elimination. The patient was started on chemotherapy but did not improve. Despite being on ART for 3 months and taking chemotherapy/radiotherapy, his CD4 counts did not rise although, his viral load was undetectable. The patient ultimately died in the 4th month of his treatment.