What is the diagnosis for a patient presenting with a rash spreading over the face and abdomen, sparing the diaper area, and having small platelets on peripheral smear?

Wiskott-Aldrich Syndrome

The diagnosis is Wiskott-Aldrich syndrome (WAS), based on the combination of a rash (eczema) involving the face and abdomen with sparing of the diaper area, and the pathognomonic finding of small platelets on peripheral smear. 1

Diagnostic Reasoning

Key Distinguishing Features

Small platelet size on peripheral smear is the most consistent and diagnostic laboratory finding in WAS. 1 Normal platelet volumes range from 7.1 to 10.5 fL, whereas WAS platelets measure 3.8 to 5.0 fL—this finding is virtually pathognomonic when combined with thrombocytopenia and eczema. 1

The rash distribution pattern is critical here:

• Eczema in WAS can be absent, mild, or severe, and commonly affects the face and trunk while characteristically sparing the diaper area. 1
• This distribution pattern, combined with small platelets, essentially confirms WAS over atopic dermatitis. 1

Why Not Atopic Dermatitis?

Atopic dermatitis does not cause thrombocytopenia or small platelets. 1 While the rash distribution could overlap, the hematologic findings exclude this diagnosis entirely. 1

Why Not Langerhans Cell Histiocytosis?

Langerhans cell histiocytosis typically presents with seborrheic-like rash in the diaper area and scalp—the opposite distribution pattern from what's described here. [@General Medicine Knowledge] Additionally, it does not cause characteristically small platelets. [@General Medicine Knowledge]

Clinical Implications and Prognosis

WAS carries significant morbidity and mortality without curative therapy, with patients typically succumbing to overwhelming infection, massive hemorrhage, or malignancy. 1

Expected Disease Manifestations

• Recurrent infections are common, including otitis media, sinopulmonary bacterial infections, and frequent viral illnesses; opportunistic infections like PCP indicate severe immune compromise. 1
• 10-15% of patients develop malignancy, with an average age of onset around 10 years; more than 80% are lymphomas, often EBV-associated. 1
• Autoimmune complications develop in older patients, including colitis, vasculitis, and glomerulonephritis. 1

Critical Pitfall to Avoid

Up to 20% of WAS patients can develop immune thrombocytopenia either before or after splenectomy, which may confuse the diagnosis if platelet size is not carefully evaluated. 1 Always examine the blood smear directly when automated counters report normal platelet size in a suspected WAS patient. 1

Confirmatory Testing Required

Definitive molecular diagnosis should be obtained by identifying a deleterious WAS gene mutation and/or demonstrating abnormal WAS protein expression via Western blot or flow cytometry. 1, 2

Specific WAS genotypes have prognostic value—certain mutations correlate with milder disease (historically termed X-linked thrombocytopenia), though recent evidence suggests even "milder" variants carry risk for severe immune complications, autoimmunity, and malignancy. 2, 3

Immediate Management Priorities

Hematopoietic stem cell transplantation (HSCT) should be considered as definitive therapy, with the best outcomes from matched related donors. 1, 4, 5 Recent advances suggest most young patients with WAS should be offered potentially curative therapy (HSCT or gene therapy) at diagnosis rather than waiting for severe complications to develop. 2

PCP prophylaxis should be initiated immediately given the severe immune compromise. [@General Medicine Knowledge based on immunodeficiency severity described in @1