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RESUMO Introdução: Paciente com diagnóstico de paquidermoperiostose, apresentando forte manifestação cutânea, impossibilitando a correção do defeito pelas técnicas usuais de lifting facial. O lifting frontal reverso foi a técnica idealizada para o caso. É uma técnica inovadora, não havendo publicação prévia na literatura. Relato de caso: Paciente italiano, sexo masculino, 56 anos, apresentando síndrome de manifestação cutânea, em especial na região frontal da face, com pele inelástica de aspecto coriáceo, que gerava desconforto estético, ensejando um estigma sindrômico. Métodos: A técnica elaborada para este caso envolve incisão, que se inicia na raiz da hélice (ponto A), contorna o supercílio em linha sinuosa distando meio centímetro da implantação dos pelos da sobrancelha, indo até a região da glabela, curvando para a raiz do nariz e indo se encontrar com dimensões idênticas do outro lado. Do ponto A, também ascende uma linha curva inclinando-se para o sentido medial, com uma distância de 2cm. A intenção é diminuir a distância entre a área a ser tracionada e a área de incisão, a fim de obter maior tração, possibilitando assim a correção do aspecto da face em foco. Resultados: A tração caudal do retalho por incisão supraciliar possibilitou a correção do defeito em região frontal sem que houvesse alteração da linha de implantação capilar ou ascensão excessiva das sobrancelhas. Conclusão: A técnica de lifting frontal reverso foi criada para um caso específico de síndrome de paquidermoperiostose. Quando bem indicada esta técnica pode ser utilizada atingindo bons resultados. ABSTRACT Introduction: Patient diagnosed with pachydermoperiostosis, presenting a strong cutaneous manifestation, making it impossible to correct the defect by the usual facial lifting techniques. The reverse frontal facelift was the idealized technique for this case. It is an innovative technique, there being no previous publication in the literature. Case report: Italian male patient, 56 years old, with cutaneous manifestation syndrome, especially in the frontal region of the face, with leathery inelastic skin, which generated aesthetic discomfort, predisposing for a syndromic stigma. Methods: The technique developed for this case involves an incision, which starts at the root of the helix (point A), bypasses the eyebrow in a sinuous line distant half a centimeter from the implantation of the eyebrow hair, going to the glabella, curving towards the nasal root and going to meet identical dimensions on the other side. From point A, a curved line also leans towards the medial direction, at a distance of 2 cm. The intention is to reduce the distance between the area to be pulled and the incision area, in order to obtain more traction, thus enabling the correction of the aspect of the face in focus. Results: Caudal traction of the flap by a supraciliary incision made it possible to correct the defect in the frontal region without altering the capillary implantation line or causing excessive eyebrow rise. Conclusion: The reverse frontal lifting technique was created for a specific case of pachydermoperiostosis syndrome. When correctly indicated, this technique can be used to achieve good results.

Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disease mainly affecting the skeletal and skin. Two genes involved in prostaglandin degradation are known to be responsible for PHO: HPGD and SLCO2A1. HPGD gene mutation can cause PHO autosomal recessive 1 (PHOAR1). The purpose of the present study is to analyze the clinical and biochemical characteristics and HPGD gene mutations of 12 Chinese PHOAR1 patients. Twelve PHOAR1 patients from eleven families, including eleven males and one female, were enrolled in this study. Digital clubbing and periostosis came out to be the most common features, which always occur in the early childhood. We performed HPGD gene analysis and identified six novel (c.1AG, c.34GT, c.317TA, c.475GT, c.548CT and c.421+1GT) and one known (c.310_311delCT) HPGD mutations. The recurrent mutation c.310_311delCT were found in all eleven patients, suggesting it is a hotspot mutation. PHOAR1 patients are considered to have an autosomal recessive inheritance pattern. Here, in addition to nine compound heterozygous patients and two homozygous patients, we found one heterozygous patient and reviewed two heterozygous patients reported in other studies. In terms of biochemical characteristics, our PHOAR1 patients have elevated urinary prostaglandin E2 (PGE2) levels (P0.001) and decreased urinary prostaglandin E metabolite (PGE-M) levels (P=0.04) compared with healthy controls. The patients' PGE2/PGE-M (E/M) ratio came out to be lower than normal subjects (P0.001). This study provides a comprehensive description of the clinical phenotypes of Chinese PHOAR1 patients and expands the genotypic spectrum of the disease.

A 21-year-old unmarried man, born of a non-consanguineous marriage, presented to the dermatology department with progressive thickening of the facial skin and eyelids, plus increased folds over his forehead for the last 5 months. He also complained of progressive enlargement of his hands and feet, with intermittent joint pains in his wrists, elbows, and ankles, along with occasional abdominal pain. He had a hearing loss and increased sweating. (

Case Presentation A 2-year-old boy was referred to the Ankara University School of Medicine Children’s Hospital with a history of recurrent respiratory distress and cyanosis since birth. His medical history was significant for premature birth at 31 weeks via cesarean section, as an infant of a diabetic mother. There was no parental consanguinity. He was hospitalized in the neonatal ICU after birth because of respiratory distress. After receiving invasive mechanical ventilation for 4 days, noninvasive mechanical ventilation and oxygen therapy were given gradually. As a result of further investigations, he received a diagnosis of situs inversus totalis and pulmonary hypertension. He was discharged on postnatal day 53 without supplemental oxygen therapy or treatment for pulmonary hypertension. Up to the age of 2 years, the patient had a history of multiple admissions to hospital for respiratory distress, lower respiratory tract infection, and cyanosis as an inpatient and outpatient. After starting to walk, shortness of breath and coughing occurred with effort.

A 49-year-old man complained of chronic palpitation and shortness of breath, which had recently become exacerbated. A blood examination indicated severe refractory anemia and hypoproteinemia. Physical examinations revealed anemia, a systolic murmur, and spoon nails. Multiple nonspecific ileal ulcers were observed. A pathological examination indicated a small granuloma with CD68-positive histiocytes. He had a deeply wrinkled forehead, chiseled face, and clubbed fingers. Radiography revealed periostosis of the fingers and long bones in the limb. He was diagnosed with pachydermoperiostosis. SLCO2A1 demonstrated a c.1807C>T homo-mutation. He was also diagnosed with SLCO2A1-associated chronic enteropathy and thus was treated with 5-aminosalicylic acid, which temporarily improved the ileal ulcers, anemia, and hypoalbuminemia.

Objectives To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP). Design Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases. Results Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently. Conclusion Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.

Background Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement. Methods We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without. Results The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15). Conclusions Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn’s disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.

Periosteosis refers to pathological woven bone formation beneath the cortical bone of the long bones. It is an imaging hallmark of primary hypertrophic osteoarthropathy (PHO) and also considered as one of the major diagnostic criteria of PHO patients. Up to date, detailed information on bone quality changes in long bones of PHO patients is still missing. This study aimed to evaluate bone microarchitecture and bone strength in PHO patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT). The study comprised 20 male PHO patients with the average age of 27.0 years and 20 age- and sex-matched healthy controls. The areal bone mineral density (aBMD) was assessed at the lumbar spine (L

Hypertrophic osteoarthropathy (HOA) is a disease characterized by abnormal skin findings and bone deformities related to subperiosteal bone formation. The disease can be associated with major systemic manifestations (secondary form) or present with absent or less prominent systemic signs and symptoms (primary form). The primary form is called pachydermoperiostosis (PDP). Whole body diffusion weighted imaging with background suppression (WB-DWIBS) is a magnetic resonance imaging (MRI) technique that has been used to highlight whole body involvement in various entities by suppressing background body signals, and is commonly used in oncologic work-ups. In this paper, we present the case of a 23-year-old male presenting with normocytic anemia and coarse facial features, as well as biological anomalies, and we report the use of WB-DWIBS in establishing the patient's diagnosis of PDP.

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy is a rare genetic disorder characterized bypachyderma and periostosis.Acromegaly is a condition caused by excessive secretion of growth hormone leading to elevated insulin growth factor-1 levels, which is characterised by somatic overgrowth and physical disfigurement notably affecting hands and feet. We presented two cases referred with an initial diagnosis of acromegaly and were ultimately diagnosed as PDP. Case 1:A 17-years old boy presented with enlargement in both feet and hands, finger clubbing, swelling in knee joints, knee pain, coarsening at facial lines and forehead skin, and excessive sweating which increased gradually over five years. There were prominent skin folds onthe forehead, face, and eyelids. Also, there was an enlargement in both hands and clubbing at the fingers. There was marked swelling at knee joints and ankles.Genetic analysis revealed a novel homozygous variantNM_005630: c.31C>T (p.Q11*) in SLCO2A1 gene.Case 2:A 16-years old boy presented with coarsening at forehead skin and scalp, excessive sweating, and pain at elbow and knee over three years. Skin folds were prominent at forehead skin and scalp.Genetic analysis revealed a homozygous variant NM_005630.2:c.86delG(p.G29Afs*48)in SLCO2A1 gene. Such clinical presentation in corroboration with normal growth hormone level and prominent radiological abnormalities prompted us to make a diagnosis of pachydermoperiostosis.Consequently,pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis.

This study aimed to investigate the bone impairment in finger joints in PHO patients by HR-pQCT. Results showed distinguished differences in bone architecture and biomechanics parameters at DIPs between PHO patients and healthy controls using HR-pQCT assessment. Besides, serum PGE2, hsCRP and ESR levels were found negatively correlated with total vBMD. This study aimed to investigate the bone impairment in finger joints in primary hypertrophic osteoarthropathy (PHO) patients firstly by high-resolution peripheral quantitative computed tomography (HR-pQCT). Fifteen PHO patients and 15 healthy controls were enrolled in this study. Bone erosions in hands at distal interphalangeal joints (DIPs) in both PHO patients and controls were evaluated by X-ray. Bone geometry, vBMD, microstructure parameters, and size of individual bone erosion were also measured at the 3rd DIP by HR-pQCT as well. Blood biochemistry levels between the two groups were also compared. Compared to X-ray, HR-pQCT assessment were more sensitive for detection of bone erosions, with 14 PHO patients by HR-pQCT versus ten PHO patients by X-ray judged at the 3rd DIP. The average depth, width, and volume of erosions size in PHO patients were 1.38 ± 0.80 mm, 0.79 ± 0.27 mm, and 1.71 ± 0.52 mm3, respectively. The bone cross-areas including total area (+ 25.3%, p ≤ 0.05), trabecular area (+ 56.2%, p ≤ 0.05), and cortical perimeter (+ 10.7%, p ≤ 0.05) at the defined region of interest of 3rd DIP was significantly larger than controls. Total vBMD was 11.9% lower in PHO patients compared with the controls (p ≤ 0.05). Biochemical test results showed the increased levels of inflammatory cytokines, bone resorption markers, and joint degeneration markers in PHO patients. Serum prostaglandin PGE2, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) levels were found negatively correlated with total vBMD. This study demonstrated higher sensitivity of the HR-pQCT measurement at DIPs by showing the differences in architecture and biomechanics parameters at DIPs between the PHO patients and healthy controls, which would be of interest clinically to investigate bone deterioration in PHO patients.

Objective To evaluate through differential diagnosis whether hypertrophic osteoarthropathy was present on an adult macaque skeleton. Materials Skeletal remains of a well-preserved adult macaque (Macaca) of unknown species curated by the archaeology department at University College London. Methods Macroscopic and radiographic evaluation of pathological lesions. Results Widespread bilateral and symmetrical periosteal new bone growth primarily affecting the limbs was observed. Conclusion A careful differential diagnosis of the lesions and comparison with previously published cases of hypertrophic osteoarthropathy among humans and non-humans suggests this animal displays a case of Hypertrophic osteoarthropathy. Significance Only been three reported cases of HOA in non-human primates have been reported, and all were apes. This study serves as the first reported case of HOA among non-hominoid simians, providing a detailed description of the skeletal lesions to aid future with paleopathological analyses. Limitations Small sample sizes for comparison and lack of context for this specimen limits discussion of the scope of this disease among non-human primates. Suggestions for further research Re-evaluate skeletal collections which have not been subject to recent osteological and pathological analysis.

Touraine-Solente-Gole syndrome is a rare, autosomal dominant multisystem disorder arising from dysregulated prostaglandin synthesis due to underlying genetic defects. Early symptoms are related to skin and soft tissue involvement (coarse facial features, widening of wrists, etc) and may thus be overlooked unless a careful physical examination is carried out. Secondary causes of pachydermoperiosteitis must always be looked for in such patients. During evaluation, a systemic review of all organ systems should be carried out to identify asymptomatic or subclinical involvement of organ systems and identify means to avoid disease progression. Treatment options are limited to steroids and non-steroidal anti-inflammatory drugs. In the absence of definitive guidelines, clinical decisions are largely case based, with no definite duration of drug therapy or screening of potential malignancies outlined in current literature. Mental health and social rehabilitation of these patients due to their disfiguring deformities are an unmet need.

Pachydermoperiostosis (PDP) is a genetic disease characterized by digital clubbing, periostosis, and pachydermia caused by mutated HPGD or SLCO2A1. Plasma prostaglandin (PG)E2 levels are increased in these patients. However, other eicosanoids have not been quantitated. We aimed to quantitate plasma eicosanoid levels in four patients carrying SLCO2A1 mutations by high-performance liquid chromatography-tandem mass spectrometry. PGE2 level was elevated in all patients; PGD2 and 11β-PGF2 α levels were also increased in some patients, whereas eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels were decreased in all patients. Our data indicate a dysfunctional eicosanoid homeostasis and varied levels of PG in patients with a complete form of PDP carrying SLCO2A1 mutations. PGE2 levels seem to mostly affect the symptoms, with other eicosanoids possibly having a minor effect.

Primary hypertrophic osteoarthropathy (PHO) is a rare disease inherited as a recessive or irregular dominant trait and characterized by digital clubbing, pachydermia, and periostosis. Biallelic mutations in HPGD and SLCO2A1, disturbing prostaglandin E2 (PGE2 ) catabolism and leading to increased circulating PGE2 level, cause PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2), respectively. However, no causative genes have been reported for PHO autosomal dominant (PHOAD). Here, we performed Sanger sequencing and whole-genome sequencing (WGS) on DNA samples from seven Chinese PHOAD families; after excluding other single-nucleotide variants (SNVs), structural variations (SVs), and copy number variations (CNVs) in the genomes, we reported six SLCO2A1 monoallelic mutations (c.1660G>A [p.G554R], c.664G>A [p.G222R], c.1106G>A [p.G369D], c.1065dupA [p.Q356TfsX77], c.1293delT [p.S432AfsX48], and c.1807C>T [p.R603X]) in the probands and affected family members. Then, in five other PHO families with probands carrying SLCO2A1 biallelic mutations, we verified that parents with SLCO2A1 monoallelic mutations also displayed PHO manifestations, which further confirmed the pathogenicity of SLCO2A1 monoallelic mutations and illustrated the allelic nature of PHOAD and PHOAR2. Subsequently, through comparison of seven PHOAD probands and 50 PHOAR2 patients, we found onset age in puberty and skewed penetrance rate were similar in both PHO types, but symptoms and signs of PHOAD were milder, including less severe pachydermia (p = .027) and periostosis (p = .005), and less frequent cutis verticis gyrata (p = .011), acne (p = .005), arthralgia (p = .037), and anemia (p = .023). The median urinary PGE2 level in PHOAD probands was almost half that in PHOAR2 patients (PHOAD 277.58 ng/mmoL creatinine, PHOAR2 473.19 ng/mmoL creatinine; p = .038). Moreover, through the 3-month trial of oral administration of etoricoxib, an effective response similar to that we reported previously in PHOAR2 patients was observed in PHOAD probands. In conclusion, our findings confirm that SLCO2A1 monoallelic mutations are the cause of PHOAD and broaden phenotypic spectrum of PHO. © 2021 American Society for Bone and Mineral Research (ASBMR).

Several juvenile diseases affect the canine forelimb. The most common are hypertrophic osteodystrophy, panosteitis, and retained cartilaginous core. Panosteitis and hypertrophic osteodystrophy tend to be self-limiting, with a good long-term prognosis, although severe cases can develop. These diseases may recur during growth. Severe cases of hypertrophic osteodystrophy can lead to angular limb deformities and may even be fatal. Retained cartilaginous cores can be benign with no evidence of clinical signs and be found incidentally on radiographs. However, if they disrupt the distal ulnar physis, angular limb deformities may persist requiring surgical intervention with a corrective osteotomy.

Purpose To report a case of severe phlyctenular keratoconjunctivitis in a patient with pachydermoperiostosis (PDP). Methods A 29-year-old Hispanic man presented with a 1-year history of vision loss in the right eye and redness, photophobia, and pain in both eyes. Associated symptoms included enlargement of his hands and feet for 3 years, acne, and joint pain. Examination was notable for severe meibomian gland dysfunction, corneal and limbal phlyctenules in both eyes, and central stromal scarring of the right cornea. He had cystic acne of the face and a coarse, wrinkled forehead and scalp. Examination of his hands and feet revealed clubbing of the digits. Results The patient had an extensive laboratory workup that was significant for elevated erythrocyte sediment rate and C-reactive protein. X-ray of his hands and feet revealed diffuse periosteal hyperostosis with diffuse bone expansion. The patient was diagnosed with PDP with severe meibomian gland dysfunction, phlyctenular keratoconjunctivitis, and corneal scarring. His pain and photophobia resolved with medical management of the phlyctenular keratoconjunctivitis but decreased vision in the right eye persisted because of neovascularization and scarring of the cornea. Conclusions We report a rare case of phlyctenular keratoconjunctivitis associated with PDP. To our knowledge, this is the first case of PDP to initially present with vision loss.

原发性肥厚性骨关节病（primary hypertrophic osteoarthropathy，PHO）是一种以杵状指（趾）、皮肤增厚及骨膜增生为主要特征的常染色体隐性遗传性疾病。报告1例SLCO2A1基因的纯合突变c.1771CT导致的PHO合并肾性失钾患者，其父母为近亲结婚，均存在SLCO2A1基因杂合突变，其弟弟有类似临床表现，也检测出SLCO2A1基因的纯合突变。.

A 63-year-old man presented with chronic multiple joint pain and swelling. The symptoms had started in adolescence, progressed for about 10–15 years, and then became constant. There was no associated morning stiffness. Symptoms suggesting any chest or abdominal disease were absent. Family history

15-Hydroxyprostaglandin dehydrogenase is NAD-dependent catalytic enzyme involved in prostaglandin biosynthesis pathway encoded by HPGD. The pathogenic variations in HPGD cause primary hypertrophic osteoarthropathy (PHO). The objective of the present study is to identify the genetic basis in patients with digital clubbing due to PHO. We performed detailed clinical and radiographic evaluation and exome sequencing in patients from three unrelated Indian families with PHO. Exome sequencing revealed two novel, c.34G>A (p.Gly12Ser) and c.313C>T (p.Gln105*) and a known variant, c.418G>C (p.Ala140Pro) in HPGD. Herein, we add three Indian families to HPGD mutation spectrum and review the literature on variants in this gene.

Background Primary hypertrophic osteoarthropathy also known as pachydermoperiostosis is a rare genetic disorder that has often been confused with acromegaly because of similar clinical features. Vascular endothelial growth factors which have been implicated in the clinical features of pachydermoperiostosis, have also been shown to be present in chronic hepatitis and implicated in the malignant transformation of hepatitis B infection to hepatocellular carcinoma. To the best of our knowledge there is one reported case of pachydermoperiostosis with chronic hepatitis B infection. We do not imply a causal relationship between pachydermoperiostosis and hepatitis B infection because pachydermoperiostosis is a genetic disorder; however, the question is raised whether hypertrophic osteoarthropathy is one of the many extrahepatic manifestations of chronic hepatitis B infection. Case presentation A 21-year-old African (Ghanaian) man with chronic hepatitis B infection was referred to our Endocrine unit as having acromegaly with changing facial features, enlarging hands and feet, and large knee joint effusions which affected activities of daily living. He was finally diagnosed as having pachydermoperiostosis when acromegaly, rheumatological disorders, as well as cardiopulmonary disorders were ruled out. He improved with arthrocentesis, a tapering regime of steroids, non-steroidal anti-inflammatory drugs, and proton pump inhibitors. Conclusions The possible role of hepatitis B in hypertrophic osteoarthropathy, that is, secondary hypertrophic osteoarthropathy, needs to be explored; however, with digital clubbing in his father our patient is likely to have pachydermoperiostosis.

BACKGROUND The present study evaluated the effects of diazine (DZN) on collagenase-induced osteoarthritis (OA) in rats. MATERIAL AND METHODS OA was produced via intra-articular injections of collagenase type II into the knee joint. The rats were then treated with DZN (25, 50, or 100 mg/kg, p.o.) for three weeks. At the end of the protocol, all rats were evaluated for paw latency, paw edema, and knee swelling. Additionally, serum concentrations of glycosaminoglycan (GAG), alkaline phosphatase (ALP), and C-reactive protein (CRP) were determined. X-rays were performed to estimate radiological and histopathological changes in the knee joint. The expressions of antioxidant enzymes, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were estimated in the synovial tissues. RESULTS DZN treatment attenuated inflammation in osteoarthritic rats, as evidenced by decreases in paw edema and knee swelling and enhanced paw latency compared to the negative control group. Additionally, there were significant decreases in the serum levels of CRP and GAG and increases in ALP in the DZN-treated groups compared to the negative control group. The radiological and histopathological results showed that DZN protected against cartilage damage in the knee joint. Additionally, MMP levels decreased and there were significant reductions in the expressions of antioxidant enzymes and TIPMs in the DZN-treated groups compared to the negative control group. CONCLUSIONS The present findings demonstrated the chondroprotective effects of DZN via its modulation of the expressions of TIMP-1 and MMPs in the synovial tissues of osteoarthritic rats.

Summary Background Pachydermoperiostosis is a rare autosomal recessive genetic disorder characterized by the association of periostosis and pachydermia. To date, two genes involved in prostaglandin metabolism, HPGD and SLCO2A1, have been identified. Patients and methods A 7-year-old girl presented digital clubbing of the hands and feet, curved nails, hyperhidrosis, and pachydermia, as well as eczema of the trunk and limbs. The diagnosis of pachydermoperiostosis was confirmed by the detection of a homozygous mutation in the HPGD gene. The second case concerned a 41-year-old male with acral and cephalic pachydermia (cutis verticis gyrata), and palmoplantar keratoderma. Bone X-rays showed changes in the distal ends of several bones. The diagnosis of pachydermoperiostosis was confirmed by the detection of a homozygous mutation in the SLCO2A1 gene. Discussion The genotype/phenotype correlation suggests that patients with SLCO2A1 mutations will develop the symptoms later in life, but that these will be more severe, with a greater likelihood of cutis verticis gyrata and joint involvement compared with patients presenting HPGD mutations. In addition, hereditary enteropathy has recently been described in patients with SLCO2A1 mutations, which could account for the gastrointestinal picture seen in the second patient. Finally, on account of cases involving myelofibrosis associated with mutations in the SLCO2A gene, these patients should have a hematologic follow-up. Conclusion Given the genotype/phenotype correlations illustrated by these cases, it would appear useful to propose molecular diagnosis for patients presenting pachydermoperiostosis.

Touraine–Solente–Gole syndrome, also known as Pachydermoperiostosis (PDP) or Primary Hypertrophic Osteoarthropathy, is a rare hereditary disorder, which affects both bones and skin. It is characterized by a combination of dermatologic changes (pachydermia or thickening of the skin) and rheumatologic manifestations (periostosis and finger clubbing). Eyelid ptosis which is caused by thickened eyelids (blepharoptosis) is a less common symptom. We report the case of a patient with a complete form of Touraine–Solente–Gole syndrome with bilateral blepharoptosis as presenting feature.

Pachydermoperiostosis (PDP) is a rare inherited multisystem disease characterized with digital clubbing, pachydermia and periostosis. Variants in either HPGD or SLCO2A1 that interrupt the prostaglandin E2 (PGE2) pathway have been shown to be involved in PDP. Here, in addition to six confirmed variants in HPGD or SLCO2A1, we identified four novel SLCO2A1 variants in eight PDP patients from seven Chinese Han families. In addition, gastric mucosa hyperplasia was observed in all affected individuals and interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα) and receptor activator of nuclear factor kappa ligand (RANKL) expression were elevated in hypertrophic gastric mucosa. Two of eight patients who had severe arthralgia were treated with celecoxib. After three months, their arthralgia was partly relieved and IL-6, TNFα and RANKL expression were decreased in accordance with their relieved hypertrophic gastric mucosa. Our study broadens the variation spectrum of SLCO2A1 and suggests that the gastric mucosa hyperplasia might be a common characteristic of PDP. Moreover, celecoxib would be a considerable choice for PDP patients. We also revealed that IL-6, TNFα and RANKL may play important roles in the molecular mechanisms of gastric mucosa hyperplasia in PDP for the first time.

Hypertrophic osteoarthropathy (HOA) is a medical condition characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and characterized by three clinical features: digital clubbing (also termed Hippocratic fingers), periostosis of tubular bones, and synovial effusions. HOA can be a primary entity, known as pachydermoperiostosis, or can be secondary to extraskeletal conditions, with different prognoses and management implications for each. There is a high association between secondary HOA and malignancy, especially non-small cell lung cancer. In such cases, it can be considered a form of paraneoplastic syndrome. The most prevalent secondary causes of HOA are pulmonary in origin, which is why this condition was formerly referred to as hypertrophic pulmonary osteoarthropathy. HOA can also be associated with pleural, mediastinal, and cardiovascular causes, as well as extrathoracic conditions such as gastrointestinal tumors and infections, cirrhosis, and inflammatory bowel disease. Although the skeletal manifestations of HOA are most commonly detected with radiography, abnormalities can also be identified with other modalities such as computed tomography, magnetic resonance imaging, and bone scintigraphy. The authors summarize the pathogenesis, classification, causes, and symptoms and signs of HOA, including the genetics underlying the primary form (pachydermoperiostosis); describe key findings of HOA found at various imaging modalities, with examples of underlying causative conditions; and discuss features differentiating HOA from other causes of multifocal periostitis, such as thyroid acropachy, hypervitaminosis A, chronic venous insufficiency, voriconazole-induced periostitis, progressive diaphyseal dysplasia, and neoplastic causes such as lymphoma.