Pachydermoperiostosis - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Pachydermoperiostosis (PDP) is an uncommon inherited disorder characterized by mainly three features; clubbing (large fingertips), hyperhidrosis (excessive sweating), and pachydermia (thickening of facial skin). The condition usually starts during adolescence or childhood, but the onset is mostly seen during puberty, after which the disease progresses slowly. It is also referred to as primary hypertrophic osteoarthropathy (PHO).

Hypertrophic osteoarthropathy is characterized by mainly clubbed toes or fingers. It is classified into two types- primary hypertrophic osteoarthropathy (PHO) and secondary hypertrophic osteoarthropathy (SHO). PHO occurs due to genetic causes, and SHO occurs due to underlying conditions. SHO involves cardiac, pulmonary, or neurologic systems. Pachydermoperiostosis is referred to as the complete form of PHO.

Pachydermoperiostosis is also referred to as:

• Primary hypertrophic osteoarthropathy.

• PHO.

• Touraine-solente-gole syndrome.

• Rosenfeld-kloepfer syndrome.

The condition was first described by Albert Tauraine, Gole, and Solente in 1935 as a primary form of PHO and is therefore known as Touraine-solente-gole syndrome.

What Are the Causes?

Pachydermoperiostosis is a rare condition, and males are more affected than females, with a ratio of 7:1. The affected females are seen to have milder symptoms, and thus the condition is often undiagnosed. On the other hand, the symptoms in males are more severe and noticeable.

Though PHO is a genetic condition, certain non-genetic forms have also been identified.

Genetic conditions can be inherited in different patterns.

All individuals, males, and females, inherit a copy of the gene pair from the mother and another from the father. Genes contain genetic information that signals the body’s normal functioning. These genes can lead to unusual features or conditions when mutations occur. In PHO, both autosomal recessive and autosomal dominant pattern has been reported.

The two genes associated with PHO are SLCO2A1 and HPGD. HPGD mutations are linked to the autosomal recessive inheritance pattern; in such cases, it is referred to as Touraine-Solente-Gole syndrome or PHOAR1.

Recessive genetic conditions occur in cases where the individual inherits both defective genes from each of the parents. If the individual receives only one mutated gene and the other one is a normal gene, the individual becomes a carrier for the condition and will not show any symptoms. The chances for two carrier parents to pass on the condition to their offspring are 25 percent, the chance that the offspring becomes a carrier is 50 percent, and the chance to have a normal child is 25 percent.

The situation remains the same, whether the child is female or male. Closely related parents are called consanguineous parents, who are more likely to have children with autosomal recessive disorders than unrelated parents.

SLCO2A1 mutations resulting in PHO can have autosomal dominant or recessive inheritance patterns. The dominant form is called PHOAD, and the recessive form is PHOAR2. In the case of dominant genetic conditions, the inheritance of a single copy of the mutated gene can result in the condition. Males with PHOAD are more commonly and severely affected.

Blacks are more affected, which is more common among adolescent boys.

What Are the Symptoms?

Symptoms vary from one individual to another. But generally, males are found to have more severe symptoms than females. PDP affects the growth of bones and skin.

The symptoms and signs include:

• Coarse facial features.

• Thick, oily, and grooved facial skin.

• Clubbing of toes and fingers.

• Periostosis, or new bone growth, occurs mainly at the ends of long bones, resulting in joint pain.

• Excessive sweating of the feet and hands.

• Drooping eyelids.

• Long eyelashes.

• Delayed closure of fontanelles (space between skull bones).

• Extra skin on the scalp leads to ridges or grooves (cutis verticis gyrate), which mostly develop in the teenage years.

• Ulcers.

• Seborrheic dermatitis (a skin condition characterized by moist or dry scales and yellowish crust).

• Occasional diarrhea.

• Pain or swelling of large joints.

How Is the Condition Diagnosed?

The diagnosis of pachydermoperiostosis is made based on clinical features. The major diagnostic criteria include periostosis (new bone growth) and digital clubbing (clubbing of the fingers). Genetic testing is used to confirm the diagnosis. Radiographically, widening can be seen at the bone ends.

The diagnosis is made based on at least two of the following four criteria:

• Digital clubbing.

• Familialhistory of transmission.

• Skeletal manifestations like signs of periostitis (radiographic signs) or pain.

• Pachyderma (facial skin thickening).

What Is the Differential Diagnosis?

The differential diagnosis includes:

• Osteoarthopathy (conditions affecting joints and bones)

• Rheumatoid arthritis (an autoimmune disease resulting in swelling, pain, and stiffness of one or more joints).

• Psoriatic arthritis (psoriasis in combination with arthritis characterized by white and red skin patches).

• Acromegaly (an uncommon acquired slowly progressing disorder that affects adults).

• Thyroid Acropachy (swelling and thickening of feet and hands).

• Hypertrophic pulmonary osteoarthropathy (an uncommon condition characterized by digital clubbing and extra growth at the ends of long bones).

What Are the Treatment Options?

The treatment mainly focuses on symptomatic treatment, which includes managing pain and swelling.

• In the case of patients with pachyderma, the main issues are gross appearance, hyperhidrosis, and oiliness. These coarse features are mainly due to excessive mucin deposition. The condition is treated with Isotretinoin which is given in a dosage of 1 mg/kg daily till a cumulative dose of 8 g is reached.

• 6.75 to 20 percent aluminum hexachlorohydrate is used for treating hyperhidrosis.

• Plastic surgery is beneficial in correcting cutis verticis gyrata and improving facial appearance.

• For symptomatic relief in case of bone pain, NSAIDs (non-steroidal anti-inflammatory drugs), colchicine, Indomethacin, etc can be used.

• Bisphosphonates and vitamin D supplements are also given.

• Corticosteroids may be given to reduce joint and bone pain.

• Surgery may be done to manage digital clubbing.

• Genetic counseling may aid the affected and their families.

• A vagotomy, a surgical procedure in which certain vagus nerve branches are cut, reduces joint pain and swelling.

Conclusion

Pachydermoperiostosis is a rare inherited disorder characterized by digital clubbing, excessive sweating, and thickening of the facial skin. The symptoms usually start during the teenage years and progress slowly. The diagnosis is mainly based on clinical features and the radiologic evaluation of skeletal manifestations. Treatment options mainly include symptomatic treatment.