Review of idiopathic lymphocytopenia

Simon Collins, HIV i-Base

A useful report in the NEJM reviews data on idiopathic lymphocytopenia (ICL) that might be useful for HIV doctors who periodically might be contacted for their experience in managing people with suppressed CD4 counts.

The lack of mechanism to explain reductions in CD4 counts not related to HIV or use of immunosuppressants is difficult.

This study reports the clinical, genetic, immunologic, and prognostic characteristics of 91 people with ICL who were enrolled during an 11-year period. Median follow-up was 3 years (IQR: 0 to 6).

Whole-exome and targeted gene sequencing were used to identify genetic causes of ICL and reported factors associated with clinical events, responses to Covid-19 vaccinations, and mortality.

The median CD4 and CD8 counts were 80 cells/mm3 (IQR: 25 to 168) and 130 (IQR: 58 to 317), respectively. Median NK cells were 142 (IQR: 100 to 378) and B cells were 144 (IQR: 92 to 218).

The most common opportunistic infections overlapped with those reported in advanced HIV and included:

  • Severe skin or anogenital human papillomavirus (HPV)–related diseases (n=27 patients).
  • Cryptococcosis (n=22 patients), which presented as meningoencephalitis, pneumonia, and disseminated skin or musculoskeletal diseases.
  • Molluscum contagiosum (n=8).
  • Disseminated nontuberculous mycobacterial infection (n=2).
  • Disseminated histoplasmosis (n=2) and pulmonary histoplasmosis (n=2).
  • Progressive multifocal leukoencephalopathy (PML) (n=3).
  • Cytomegalovirus diseases (colitis and retinitis in 1 patient each).
  • Pneumocystis jirovecii pneumonia (PJP), oral candidiasis, pulmonary coccidioidomycosis, and pulmonary aspergillosis were observed in 1 patient each.

A total of 21 of 53 people (40%) had at least two different opportunistic infections.


Although idiopathic lymphocytopenia is by definition not related to HIV, the i-Base information service has also been contacted by people with significant and progressive immune suppression.

For some reason, these individuals have great difficulty getting access to prophylaxis medicines used in the management of advanced HIV.


Lisco A et al. Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years. N Engl J Med 2023; 388:1680-1691. DOI: 10.1056/NEJMoa2202348. (4 May 2023).

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