Pachydermoperiosteosis, primary M89.4

Clinical picture characterized by hyperostoses of the skeleton, pachydermia and drumstick fingers/clock's neck nails.

Inherited irregularly in an autosomal dominant manner, rarely sporadic.

Tariq et al (2009) performed linkage analysis in a 6-generation Pakistani family with isolated congenital clubbing in which 11 affected members (4 males and 7 females) had bilateral symmetric clubbing on all finger and toe nails without associated abnormalities. Genome-wide mapping revealed that all affected individuals were homozygous at marker D4S2368 on chromosome 4q32.3.

Also described are germline mutations in the HPGD gene, which encodes 15-hydroxyprostagladin dehydrogenase. The enzyme defect leads to an increase in serum prostaglandin (PgE2) levels. Prostagalndin E2 affects bone metabolism via stimulation of osteoblasts and osteoclasts and enhances peripheral vasodilation.

Apparently, a mutation in the SLCO2A1 gene, a GEn encoding a prostaglandin transporter, also leads to an analogous phenotype.

Predominantly in adolescents, especially males; less often in childhood or in adults. More common in people with dark skin colour.

Symmetrical periosteal thickenings, especially distal to the long tubular bones, soft tissue thickenings in the face in the sense of cutis verticis et frontis gyrata, on arms and legs, keratosis palmoplantaris and hyperhidrosis, drumstick-like fingers and toes, acrocyanosis and seborrhoea. It is not uncommon for severe acne to occur pre- or post-pubertal.

Surgical treatment of the skeletal changes and plastic surgery of the pachydermic skin areas. Isotretinoin (e.g. isotretinoin-ratiopharm; acnenormin) 0.5-1.0 mg/kg bw/day p.o. can be used to reduce sebaceous gland production, maintenance therapy 0.2-0.5 mg/kg bw/day or less, depending on the clinic. Iontophoresis for the treatment of hyperhidrosis.

Exclusion of secondary pachydermoperiostosis (tumour search!).

1. Brilon C et al (1990) Pachydermoperiostosis. Akt Dermatol 16: 353-356
2. Fietta P, Manganelli P (2003) Pachydermoperiostosis and psoriatic onychopathy: an unusual association. J Eur Acad Dermatol Venereol 17: 73-76
3. Friedreich N (1868) Hyperostosis of the entire skeleton. Arch Path Anat 43: 83-87
4. Jansen T et al (1995) Pachydermoperiostosis. Dermatologist 46: 429-435
5. Tariq M et al (2009) Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC). J Med Genet 46: 14-20.
6. Thappa DM et al (2000) Primary pachydermoperiostosis: a case report. J Dermatol 27: 106-109
7. Touraine A, Solente G, Gole L (1935) Un syndrome osteodermopathique: la pachydermie plicaturee avec pachyperiostose ds extremites. Presse Med 43: 1820-1824