Painful Joint Contractures Research Articles

Infantile systemic hyalinosis: report of a case from Bahrain and review of literature

Background: Infantile systemic hyalinosis (ISH), an allelic form of hyaline fibromatosis syndrome, is a rare fatal autosomal recessive disorder that is caused by mutations in the CMG2/ANTRX2 gene encoding the transmembrane anthrax toxin receptor 2. It has a compound of features due to the accumulation of hyaline material in multiple organs including characteristic skin lesions, joint contractures, persistent diarrhea, and failure to thrive. The resulting severe malnutrition can be the cause of death in early infancy. Due to its rarity and early high fatality rate, timely diagnosis is difficult, and children with ISH may die undiagnosed. Case Presentation: In this report, we describe a 3-year-old female diagnosed with ISH after reviewing her clinical and laboratory workup in Salmaniya Medical Hospital. She was diagnosed with ISH based on the clinical presentation of severe skin lesions, painful joint contractures, and later developed renal tubular acidosis. Her diagnosis was confirmed with skin histopathology and identification of homozygous ANTRX2 mutation, c.652T>C, p.Cys218Arg, and Chr4 (GRCh37): g.80957171A>G. Conclusion: While the clinical outcome of the disease is poor without curative treatment, establishing an early diagnosis of ISH, beginning with clinical suspicion to molecular analysis, is important for accurate management as well as carrier and risk assessment of family members.

Protein-losing enteropathy and joint contractures caused by a novel homozygous ANTXR2 mutation.

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disorder and an allelic form of hyaline fibromatosis syndrome that is caused by mutations in the ANTRX2 gene encoding the transmembrane anthrax toxin receptor 2. Its main features include characteristic skin lesions, joint contractures, persistent diarrhea, and failure to thrive due to accumulation of hyaline material in multiple organs. The resulting severe malnutrition can cause death in early infancy. Because of its rarity and high fatality rate, timely diagnosis is difficult and ISH may be underdiagnosed. In this report, we describe a 10-month-old male with severe protein-losing enteropathy, skin lesions, and painful joint contractures, diagnosed with ISH based on skin his-topathology and identification of a novel homozygous ANTRX2 mutation, c.1127_1128delTG (p.V376Gfs*14). While its clinical outcome is poor without curative treatment, establishing a diagnosis of ISH starting from clinical suspicion to molecular analysis is important for appropriate medical management and for risk and carrier assessment of family members.

Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis syndrome: a rare cause of protein-losing enteropathy

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disease. Typically, ISH patients present with progressive painful joint contractures, intractable diarrhea, hyperpigmented skin lesions, and perianal fleshy nodules. We report a case of a 19-month-old male child with atypical ISH presentation. His main clinical finding was protein-losing enteropathy due to intestinal lymphangectasia. This report is intended to enhance awareness about the gastrointestinal tract presentation of ISH.

Familial Arthropathy in Saudi Arabian Children: Demographic, Clinical, and Biochemical Features

Familial arthropathy comprises a heterogeneous group of arthropathies. It can be either an inflammatory or a noninflammatory condition. The worldwide frequency of these disorders is unknown. To study the demographic, clinical and biochemical features, and survival of a large series of children with familial arthropathies. The medical records of children who had an arthropathy and a family history of a similar condition at the Pediatric Rheumatology Clinic at King Faisal Specialist Hospital-Riyadh between 1990 and 2005 were reviewed. These included children with familial juvenile idiopathic arthritis (FJIA), infantile systemic hyalinosis (ISH), the nodulosis-arthropathy-osteolysis (NAO) syndrome, and the camptodactyly-arthropathy-coxa vara (CAC) syndrome. Familial rheumatic diseases including spondyloarthropathies or known syndromes associated with articular manifestations were excluded. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, and provisional and final diagnoses as well as treatment and outcome were reviewed. Sixty-two children with various familial arthropathies were reviewed. Twelve children (9 female/3 male) with FJIA presented with polyarthritis. These children belonged to 4 unrelated families, all of whom were from the same geographical area, with 2 families belonging to the same tribe. The mean age at onset was 2.4 years, and mean age at diagnosis was 3.5 years. All children had high inflammatory markers. Nineteen children (11 male/8 female) with ISH presented in the neonatal period with painful joint contractures and typical mucocutaneous features. The referral diagnosis was inaccurate in 14 patients. Thirteen patients were the product of first-degree cousin marriages, and 5 families had more than 1 affected child. Radiological findings included periosteal reaction and osteolytic lesions. Tissue biopsy was performed in 8 patients and the findings were consistent with the diagnosis in all 8 patients. Despite aggressive management, 16 patients died. The mean age of the remaining 3 surviving children was 20 months. There were 15 children (9 female/6 male) with the NAO syndrome with a mean age at onset of 3.4 years. They were from 7 unrelated families; 5 families had more than 1 affected child. The referral diagnosis was juvenile idiopathic arthritis (JIA). Most children presented with painful deformed hands. Eleven children (70%) had advanced osteolytic changes. All children had normal inflammatory markers. There were 16 children (11 male/5 female) with the CAC syndrome who were diagnosed at a mean age of 3.7 years. Camptodactyly presented at birth or in first months of life, while other features developed in early childhood. JIA was the referral diagnosis. Fourteen children had bilateral coxa vara. Two children exhibited symptoms or signs of pericarditis. Inflammatory markers were normal in all children. Familial arthropathies are not uncommon conditions which may be easily confused with JIA, causing a delay in diagnosis and management. Careful evaluation of a child presenting with an arthropathy, particularly in a population where consanguinity is common, is required for timely and accurate diagnosis. Overall, the prognosis of these conditions remains guarded despite treatment.

Infantile systemic hyalinosis: report of three Iranian children and review of the literature

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disease characterized by diffuse hyaline deposits in the skin, gastrointestinal tract, muscle and endocrine glands. The clinical features are evident either at birth or within 6 months of life. The disease is manifested by painful progressive joint contractures, thick skin with hyperpigmentation, susceptibility to bone fractures, infections, failure to thrive and persistent diarrhea due to protein-losing enteropathy. Here, we report three unrelated Iranian children with a limited range of joint movements in the first month of life, skin hyperpigmentation and painful joint contractures. Pathological findings also confirmed the diagnosis of ISH in these patients.

Infantile Systemic Hyalinosis: report of three unrelated Brazilian children and review of the literature

Infantile Systemic Hyalinosis (ISH) is an autosomal recessive disorder characterized by diffuse hyaline deposits in the skin, gastrointestinal tract, muscles and glands. Recently, mutations in the capillary morphogenesis gene-2 (CMG-2), a transmembrane protein with important roles in cell-cell adhesion and cell-extracellular matrix interactions, have been shown to cause ISH. We report on three unrelated Brazilian children presenting in the first days of life with a limited range of joint movements, progressing to painful joint contractures. Additional findings included skin hyperpigmentation over small joints, enlargement of major joints, rigid vertebral spine, thickened skin, facial papuloerythematous rash, and cervical, dorsal and perianal nodules. Skin biopsy performed in all three patients showed diffuse deposits of hyaline material, confirming the diagnosis of ISH.

ARTICULAR DAMAGE IN SJOGREN’S DISEASE

Objective. To give clinical and x-ray characteristics of joint syndrome in Sjogren's disease. Methods. 150 patients with Sjogren's disease were included. Clinical and retrospective radiological examinations were performed. Progression of hands and feet joints radiological damage was assessed using Larsen's scale. Results. Arthralgia was present in 76%, light morning stiffness - in 42,7% (more often lasting less then 20 min), Al the admission arthritis was noted in 16,7%. Hand small joints damage was prevalent. 36% of patients had history of arthritis. Its development was accompanied by purpura in one third of cases. Painful hand joint contractures were noted in 9,3%, diffuse hands oedema in 4,6%, ulnar deviation of the metacarpophalangeal joints in 0,7%, Jaccoud's arthropathy in 0,7%. Single surface erosions of hands were revealed at the X-ray examinations in 7 patients (4,7%). Early development of osteoarthrosis was noted. Larsen index ranged from 0 to 29 at the first and from 0 to 37 at the second examination (after 4.7 years). Conclusion. Joint syndrome in Sjogren's disease is characterized by light morning stiffness of short duration, arthritis which is usually not erosive and more often affects small joints оГ hands. Painful joint contractures and diffuse hands oedema are less frequent.

Infantile systemic hyalinosis in siblings: clinical report, biochemical and ultrastructural findings, and review of the literature.

A boy presented at age 3.5 months with joint contractures, restlessness, and pain on handling. His skin was thickened and there were livid-red macular lesions over bony prominences. Infantile systemic hyalinosis (ISH) was diagnosed, a presumably autosomal recessive, progressive, and painful disorder of as yet unknown pathogenesis. Observation over three years confirmed the diagnosis as typical changes, such as nodules on both ears, pearly papules in the perinasal folds and on the neck, fleshy nodules in the perianal region, and gingival hypertrophy, developed. Skin lesions and painful joint contractures progressed in spite of intense physiotherapy, and at age 3, the child had marked motor disability. The central nervous system (CNS) appeared to be intact and the infant showed normal mental development. Radiologic findings included marked generalized osteopenia, osteolytic erosions in the metaphyses of the long bones, and cortical thinning. Electron microscopy of two skin biopsies demonstrated deposition of floccular amorphous substance that was abundant around, and appeared to originate from, small blood vessels in the dermis, partially interfering with collagen fiber formation. Lysosomal inclusions were not seen. Serum acid hyaluronidase activity was within the normal range, and the synthesis of hyaluronic acid and proteoglycans in cultured skin fibroblasts was similar to that of control cells. A younger sister presented at age two months with painful joint contractures and discrete livid-red macules over both malleoli, and showed a similar progression of the disorder over the first year of life. The diagnosis of ISH should be considered in infants and children presenting with painful joint contractures and skin lesions. The pathogenesis of this disabling and disfiguring disorder remains unclear. Our data confirm probable autosomal recessive inheritance, and do not support lysosomal storage, hyaluronidase deficiency, or a primary collagen disorder, but indicate that the amorphous material accumulating in the skin and articular soft tissues may originate from the blood circulation.