Primary Hypertrophic Osteoarthropathy

Primary hypertrophic osteoarthropathy (PHO) is a genetically and clinically heterogeneous inherited disorder characterized by digital clubbing and osteoarthropathy, with variable features of pachydermia, delayed closure of the fontanels, and congenital heart disease. There are two types of PHO: pachydermoperiostosis and cranio-osteoarthropathy (see these terms).

Epidemiology

Prevalence is unknown. Cranio-osteoarthropathy is the rarest form, with about 30 cases reported to date.

Clinical description

Patients typically present in infancy with clubbing, hyperhidrosis, bone and joint pain and skin thickening. The clinical constellation of PHO includes skin thickening and excessive sweating (pachydermoperiostosis), delayed closure of the cranial sutures (cranio-osteoarthropathy) and congenital heart disease, especially patent arterial duct (see this term).

Etiology

Mutations in the HPGD gene (4q33-q34) encoding 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the main enzyme of prostaglandin degradation, have been identified.

Diagnostic methods

Diagnosis is based on clinical signs and X-ray exam, magnetic resonance imaging (MRI) or radionucleotide bone imaging showing typical bone abnormalities, such as diaphyseal periostosis and acro-osteolysis.

Differential diagnosis

Differential diagnoses include secondary hypertrophic osteoarthropathy, chronic recurrent non-bacterial osteomyelitis, SAPHO and Camurati-Engelman syndromes (see these terms) and chronic bacterial osteomyelitis.

Genetic counseling

PHO is inherited as an autosomal recessive trait; however, heterozygous carriers can have a mild phenotype. Since mutations in the HPGD gene have recently been reported, genetic counseling and prenatal diagnosis might be considered.

Management and treatment

Rheumatological symptoms can be improved by nonsteroidal anti-inflammatory drugs, which have been shown to directly influence the pathogenesis. In addition, corticosteroids or colchicine have been tried. Clinical improvement of the dermatological symptoms is achieved by retinoids. Plastic surgery may be helpful for facial involvement. Finger clubbing surgical reduction has been tried with success.

Prognosis

PHO progresses constantly, leaving patients with chronic debilitating complications, such as clubbing and arthritis.