Discussion:
WHIMS is an autosomal dominant IEI caused by a gain of function mutation in CXC chemokine receptor 4 (CXCR4) 1. CXCR4 chemokine receptor binds to its ligand CXCL-12 and has a role in leukocyte trafficking, signaling, survival and proliferation 2. Clinical spectrum of WHIMS includes recurrent infections, susceptibility to human papilloma virus (HPV) infection, and immunodeficiency characterized by neutropenia, hypogammaglobulinemia, and lymphopenia.
Common hematological manifestations observed in WHIMS include neutropenia, lymphopenia, and mild thrombocytopenia3,4. Neutrophils are typically sequestered within the bone marrow that show myeloid hyperplasia and cytoplasmic abnormalities like vacuolization, chromatin hyper condensation and hyper segmented nuclei, traditionally labelled as myelokathexis 3.
Because of rarity of this condition, WHIMS is often overlooked and missed by hematologists during the evaluation of panleukopenia or neutropenia 5. In majority of centers, CXCR4 is not included in the panel for genetic evaluation of leukopenia/ neutropenia. Our patient was evaluated for chronic leukopenia for months elsewhere. The bone marrow examination also missed myelokathexis and genetic testing finally clinched the diagnosis of WHIMS.
Treatment involves antimicrobial therapy, removal of warts and immunoglobulin replacement in patients with hypogammaglobulinemia. Leucocyte mobilizing agents like G-CSF and specific CXCR-4antagonists like plerixafor are advised in patients with severe neutropenia and recurrent infections 6. Definitive cure strategies include allogenic hematopoietic stem cell transplant and gene therapy 4 .
In conclusion, WHIMS is an important differential diagnosis to be considered in evaluation of leukopenia in childhood. A careful look at marrow for myelokathexis or a genetic work-up can clinch the diagnosis of WHIMS in children with leukopenia. Genetic confirmation is essential for counselling of the affected families.