PDP or Touraine-Solente-Gole syndrome is the primary form of HOA. Although an autosomal dominant inheritance with incomplete penetrance and variable expression has been confirmed, both autosomal recessive and X-linked inheritance has been suggested [7]. PDP is related to mutations of the gene encoding for 15-hydroxyprostaglandin dehydrogenase (15HPGD) [10]. PDP patients have high levels of PGE2 and decreased levels of PGE-M (the metabolite of PGE2). PGE2 can mimic the activity of osteoblasts and osteoclasts, which may be responsible for the acro-osteolysis and periosteal bone formation [11]. PGE2 also has vasodilatory effects, which may be responsible for prolonged local vasodilation resulting in digital clubbing [11]. A familial history is found in 25 to 38 percent of patients. Our patient did not have family history.

PDP makes 3%‐5% of cases of hypertrophic osteoarthropathy and should be distinguished from the secondary formbefore a diagnosis of PDP is established [18]. The secondary form usually results from cardiopulmonary diseases (eg,bronchiectasis, cystic fibrosis, congenital heart diseases, andtuberculosis), hepatic diseases (eg, portal and biliary cirrhosis),gastrointestinaldiseases(eg,inflammatoryboweldisease andpolyposis), andcertain malignancies (eg, Hodgkin'sdisease,nasopharyngealcarcinoma, andchronicmyeloidleukemia).Clinically, insecondaryform,thecutaneousfindings(pachydermia,seborrhea, oiliness)are lessfrequentthanprimary PDP;theosteoarthropathy ismoresevere and painful,especiallywithcongenitalcyanoticheartdisease [19]. In secondary form due to neoplasia, only treatment of the underlyingillness causesimprovementofthe associatedsymptoms [20].

Other differential diagnoses include acromegaly, thyroid acropachy, van Buchem's disease (in which there is absence of clubbing and skin changes), psoriasis, and rheumatoid arthritis. Patientswithforme frusta have to be differentiatedfrom the rare hyperelasticity disorderssuch as Ehler‐Danlossyndrome, cutislaxa,Meretoga'ssyndrome,Marfan'ssyndrome, andpseudoxanthomaelasticum,whichmay causeforeheadfurrows [21].

In up to 30% of the patients, PDP presents as a hereditary disease with autosomal dominance of variable penetrance. Although pathogenesis iscurrentlyunknown, anincreased level of prostaglandin E2 whichmotivatestheoverexpression of the vascular endothelial growthfactor hasbeen proposed asamain factor. Duetohigh M:Fratio,X‐linkedtransmission androle oftestosteronehormonehavebeensuggested asotherfactors [22]. Recently, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organicanion transporter family member 2A1 (SLCO2A1) weredescribed as pathogenic genes responsible for PDP. Whengermline SLCO2A1 mutations are detected, myelofibrosis,a life‐threatening complication, should be suspected and individualfollowed upperiodically. Alcoholicconsumption might be a contributing factor by alteration of prostaglandin metabolism [23]. Unfortunately, genetic testing for our reported case was not available at our center.

The diagnostic criteria for pachydermoperiostosis [9,24] are:

Major criteria: pachyderma, periostosis, finger clubbing.

Minor criteria: hyperhidrosis, arthralgia, gastric ulcer, cutis verticis gyrate, blepharoptosis, joint effusion, column-like legs, edema, seborrhea, acne, flushing. Our patient had all three major criteria i.e., hyperostosis, finger clubbing, and pachyderma. Martinez-Lavin [13] proposed the pathology for pachydermoperiostosis is due to increased amount of proliferation of collagen fibers from actively proliferating fibroblasts.

Pachydermia [25]—which affects the face and limbs—is the most frequent skin symptom.

The grading of pachyderma is as follows – grade 0:- absence, grade 1:- mild to moderate involvement (cutaneous thickening without puckering), grade 2:- severe (cutaneous thickening and puckering). Patients may also present with seborrhea (90% of cases), acne, folliculitis, dilated pores, hyperhidrosis of the palms and soles (44–67% of cases) may be associated with flushing, thickened eyelids (30–40% of cases), cutis vertices gyrate (24% of cases), and reduced facial and pubic hair.

Digital clubbing is seen in 89% of cases and nail bed capillary microscopy shows slight capillary enlargement and increased tortuosity. Arthritis is seen in 20–40% of cases²⁶ and a joint effusion is seen in 41%. Irregular periosteal ossification affects predominantly the distal ends of long bones seen in 80–97% of patients.

A range of processes (some malignant) has been reported in association with pachydermoperiostosis. These include facial epidermoid carcinoma, [20] hypertrophic gastritis, peptic ulcer, gastric adenocarcinoma, [27] Crohn’s disease, and myelofibrosis [28]. As a consequence of increased soft tissue bulk and hyperostosis, complications may arise such as ptosis, compression of the nerve endings, hearing problems, kyphosis, arthrosis, osteonecrosis of the femoral head, and carpal tunnel syndrome. Variants of pachydermoperiostosis include Rosenfeld-Kloepfer syndrome (characterized by enlargement of the jaws, especially mandible, and of the hands and feet, nose, lips, tongue, and forehead, along with cutis vertices gyrata and corneal leukoma); Currarino idiopathic osteoarthropathy (an incomplete form of PDP seen in children and adolescents and characterized by the presence of eczema and sutural diastases); and a localized form with only the radiographic features of PDP in the lower extremities.

The diagnosis was confirmed by histopathological study.Histopathological examination of skin samples takenfrom patients with PDP shows epidermal acanthosis and hyperkeratosis,differentdegrees offibrosis andcapillaryectasia ofthedermis aswell as sebaceousglandhypertrophy.Bone biopsy showed cortical hyperostosis and thickening ofthe periosteum with bands of partially hyalinized connectivetissue in addition to vascular hyperplasia, with a reduction intrabecular bone. In cases with arthritis, the synovial membraneshowedvascularcongestionandstromal edema, lymphocyticandmonocyticinfiltration, andformationofsolitarylymphaticfollicles [29,30]. Radiographs of the hands and feetshow joint space narrowing, swelling in the soft tissues, andacro‐osteolysis of the distal phalanges. There is also symmetricalperiostosisthat ismoreprominent inthedistallowerlimbs [31].

This syndrome can be distinguished from acromegaly on the basis of clinical features and laboratory findings. In contrast to PDP, acromegaly presents clinically with larger bones in the face, skull and limbs, jaw prognathism, along with elevated insulin-like growth factor-1 levels and positive oral glucose tolerance test [32,33,34]. Acromegaly is often caused by a pituitary tumor, and thepotential manifestations of the tumor’s local compressionand hormonal disruption additionally help to distinguishit from PDP. In our patient, closer scrutiny in theclinical examination coupled with the negative biochemicalmarkers for acromegaly effectively allowed us to ruleout this differential.

The case presented here is a complete form of the syndrome, withthepresence ofmost ofthe clinical characteristic and radiologicalfindings. The patient hadsignificant joint involvement and severedigital clubbing, and the presence of bonyexcrescences was detected intheX‐rays ofhishands andfeet. Inthis case, cutisverticisgyrateaffectedonly hisforehead andsmallarea ofthescalp.Furthermore,althoughthissyndrome has astrong associationwithheredity, inthis case,therewas noreport ofrelativeswithsimilarcharacteristics.

No specific treatment exists; however, in most cases, PDP tends to stabilize over time. Conventional PDP drug treatments to decrease inflammation and pain include aspirin, NSAIDs and corticosteroids [35]. Rheumatologic symptoms can be improved by treatment with bisphosphonates, such as pamidronate or risedronate [35]. In isolated cases, tamoxifen was effective in PDP treatment, especially for bone and joint pain [35]. Retinoids are used to improve skin manifestations. Isotretinoin improves cosmetic features by inducing apoptosis within human sebaceous glands. As a result, the increase of connective tissue and hyperplasia of sebaceous glands is inhibited. Retinoids also decrease procollagen mRNA in fibroblasts, improving pachyderma and cutis verticis gyrate [36,37]. Colchicine can also improve articulr symptoms and skin manifestations such as folliculitis, and pachyderma [35]. The use of Botulinum toxin type A (BTX-A) may improve the leonine facies. Da costa et al reported the use of infliximab in a patient with refractory arthritis [38]. Surgical methods, including facelifts and facial rhytidectomy, have also been used to improve facial appearance [39].