When Myelofibrosis is Skin-Deep: A Clinical Clue to a Rare Diagnosis

A 24-year-old male presented with an 8-year history of transfusion-dependent anemia.Complete blood counts revealed pancytopenia with hemoglobin 6.9 g/dL, white blood cell count 2.1 10/L, and platelet count 80 10/L.Examination showed grade 2 clubbing, coarse facial features, and skin thickening over face, hands, and soles (Figure 1).Radiographic imaging revealed acro-osteolysis of the digits, cortical thickening of long bones, and symmetrical shaggy periosteal new bone growth (Figure 2).Clinical examination was not suggestive of any pulmonary condition and 2D Echo ruled out cardiac pathologies.Bone marrow biopsy demonstrated grade 3 reticulin fibrosis (Figure 3).Testing for JAK2, CALR & MPL was negative.Clinical exome sequencing identified a homozygous SLCO2A1 mutation (exon 11, p.Leu516SerfsTer12), confirming pachydermoperiostosis (PDP).Treatment with prednisolone and etoricoxib leads to increase in hemoglobin up to 9g/dL & he became transfusion independent till the last follow up (18 months from diagnosis).The three hallmarks of PDP are periosteal new bone growth, digital clubbing, and pachydermia [1].Mutations in SLCO2A1 impair cellular uptake of prostaglandin E2 (PGE2), preventing its intracellular degradation.The elevated PGE2 causes periostosis, digital clubbing, and skin thickening [2].Selective COX-2 inhibitor Etoricoxib & prednisolone has shown some efficacy in improving anemia and reducing fibrosis [3,4].This case emphasises the importance of careful physical examination in young patients with unexplained myelofibrosis & identification of SLCO2A1 mutation has therapeutic relevance.