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.