Fibrodysplasia ossificans progressiva in South Africa: difficulties in management in a developing country.

Fibrodysplasia ossificans progressiva is a rare genetic disorder in which progressive ossification of connective tissue leads to severe disability. The condition is an autosomal dominant trait, and most of the affected persons represent new mutations for the determinant gene, ACVR1, chromosomal locus 2q23-24. Although fibrodysplasia ossificans progressiva has a worldwide distribution, there are only a few reports of affected persons of indigenous African stock. We studied and documented 3 affected individuals in the African (Xhosa) community from South Africa. In addition to describing the manifestations and natural history of the disorder in Africa, we discuss the challenge of management of this condition in the South African context.

Long-term effectiveness and safety of infliximab, golimumab and ustekinumab in patients with psoriatic arthritis from a Canadian prospective observational registry.

OBJECTIVES: The objectives of this study were to describe the demographic profile and baseline disease characteristics of patients with psoriatic arthritis (PsA) treated with either infliximab (IFX), subcutaneous golimumab (GLM) or ustekinumab (UST) treatment in Canadian routine care setting along with assessing long-term effectiveness and safety. METHODS: Patients with PsA were enrolled into the Biologic Treatment Registry Across Canada registry (ClinicalTrials.gov Identifier: NCT00741793) from 2005 to 2017. The study visits occurred at study enrolment (baseline) and every 6 months thereafter. Effectiveness was assessed by changes in disease parameters (joint counts, Psoriasis Area Severity Index (PASI), Health Assessment Questionnaire, patient/physician global, minimal disease activity, enthesitis, dactylitis, erythrocyte sedimentation rate, C reactive protein). Improvements from baseline were explored with the paired t-test and the McNemar's test. Safety was evaluated by assessing the incidence of adverse events (AEs) and drug survival rates. RESULTS: A total of 111 IFX-treated, 281 GLM-treated and 70 UST-treated patients were enrolled. Most baseline disease parameters remained similar over time in all three cohorts. UST-treated patients had lower mean baseline Disease Activity Score in 28 joints CRP, swollen joint based on 28 joints and higher PASI compared with patients treated with GLM. Treatment with IFX, GLM and UST was associated with significant improvements in all disease parameters over time (p<0.001) from baseline up to 84, 84 and 40 months, respectively.AEs were reported for 74.8%, 69.8% and 52.9% (138, 114 and 115 events/100 patient-years (PYs)) covering 325, 567 and 87 years of exposure for IFX-treated, GLM-treated and UST-treated patients, respectively. Severe AEs were reported in 19.8%, 8.5% and 5.7% (8.8, 7.2 and 8.0 events/100 PYs) in IFX-treated, GLM-treated and UST-treated patients, respectively. The proportion of patients who discontinued treatment were 63.1%, 50.9% and 50.0%, respectively. CONCLUSIONS: IFX, GLM and UST treatment significantly reduced disease activity and improved functionality in patients with PsA followed by routine clinical practice and had a safety profile similar to that previously reported in the literature. TRIAL REGISTRATION NUMBER: NCT00741793.

Hereditary bone dysplasia with pathological fractures and nodal osteoarthropathy.

A father and daughter both had multiple pathological fractures and nodal osteoarthropathy. The father, aged 50 years, had at least 20 healed fractures of the axial and appendicular skeleton, sustained by minor trauma over his 50-year lifespan, many of which had been surgically fixed prior to his first presentation to us. Fractures of the clavicles, thoracic cage and long bones of the arms and legs, had healed with malalignment and deformity. Healed fractures were complicated by ankylosis of the cervical vertebrae and both elbows. He also had osteoarthritis of the hands, with exuberant osteophytosis, and profound perceptive deafness. His general health was good, his intellect and facies were normal, and his sclerae were white. The daughter, aged 27 years, had sustained at least seven fractures of the axial and appendicular skeleton following trivial injuries, in distribution similar to those of the father.She had also experienced painful swelling of the fingers,which preceded progressive development of nodal osteoarthropathy.Her hearing was normal. In both individuals,biochemical and immunological investigations yielded normal results. It was not possible for molecular studies to be undertaken. Pedigree data were consistent with autosomal dominant transmission, and this disorder appeared to be a previously undocumented heritable skeletal dysplasia.

Poncet's Disease in the Preclinical Phase of Rheumatoid Arthritis.

We report on a patient with seropositive polyarthritis retrospectively diagnosed as Poncet's disease in the preclinical phase of seropositive rheumatoid arthritis. Our patient developed rheumatoid arthritis more than 2 years after being successfully treated for pulmonary tuberculosis and an initial inflammatory polyarthritis consistent with the diagnosis of Poncet's disease. This case illustrates the importance of recognizing Poncet's disease in a patient presenting with polyarthritis in order to avoid inappropriate long-term disease modifying antirheumatic treatment. It also illustrates the need for adequate follow-up of patients with Poncet's disease after treatment with antituberculosis treatment so that progression to a primary inflammatory arthritis such as rheumatoid arthritis may be identified timeously. Although seropositivity for rheumatoid arthritis has been reported in Poncet's disease as well as in tuberculosis, it is rather uncommon, and long-term follow-up of patients with Poncet's disease is essential particularly if they have positive serological tests for rheumatoid arthritis. In this case report, we describe the first reported case of Poncet's disease in the preclinical phase of rheumatoid arthritis and review the literature related to this rare disease presentation.

Reduced eccentric loading of the knee with the pose running method.

PURPOSE: The aim of this study was to compare the biomechanical changes during natural heel-toe running with learned midfoot and Pose running. METHODS: Twenty heel-toe runners were instructed in midfoot running and a novel running style in which the acromium, greater trochanter, and lateral malleolus are aligned in stance (Pose running). Clinical gait analysis was performed for each running style and the biomechanical variables compared. RESULTS: In comparison with midfoot and heel-toe running Pose running was characterized by shorter stride lengths and smaller vertical oscillations of the sacrum and left heel marker. Compared with midfoot and Pose running heel-toe running was characterized by greater magnitudes and loading rates of the vertical impact force. In preparation for initial contact, the knee flexed more in Pose than in heel-toe and midfoot running. The ankle at initial contact was neutral in Pose compared with a dorsiflexed and plantarflexed position in heel-toe and midfoot running, respectively. The knee power absorption and eccentric work were significant lower (P < 0.05) in Pose than in either heel-toe or midfoot running. In contrast, there was a higher power absorption and eccentric work at the ankle in Pose compared with heel-toe and midfoot running. CONCLUSIONS: Pose running was associated with shorter stride lengths, smaller vertical oscillations of the sacrum and left heel markers, a neutral ankle joint at initial contact, and lower eccentric work and power absorption at the knee than occurred in either midfoot or heel-toe running. The possibility that such gait differences could be associated with different types and frequencies of running injuries should be evaluated in controlled clinical trails.

Confirmation of the recurrent ACVR1 617G>A mutation in South Africans with fibrodysplasia ossificans progressiva.

OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition in which progressive ossification of fibrous tissue, tendons and ligaments leads to severe physical handicap. Most affected individuals who have been studied have a recurrent 617G>A mutation in the ACVR1/ALK2 gene that codes for activin A type 1 receptor/activin-like kinase 2. The majority of publications on the genetics of FOP have concerned whites or Asians, and no genetic information is available concerning sub-Saharan blacks. The aim of the project was to determine whether or not this mutation is present in affected persons in South Africa. METHOD: Molecular mutational analysis was undertaken on genomic DNA from peripheral blood leukocytes from 6 affected South African of different population groups (4 Xhosa, 1 coloured, 1 white). RESULTS: The 6 persons with FOP were all heterozygous for the ACVR1/ALK2 617G>A mutation. This mutation was absent in 6 controls. CONCLUSION: Confirmation of the presence of this recurrent mutation facilitates diagnostic accuracy in affected persons in South Africa, and allows researchers to narrow the search for molecular targets for rational intervention to the ACVR1/ALK2 domain.

An atropine and glycopyrrolate combination reduces mortality in organophosphate poisoning.

Anticholinergics are the mainstay of the pharmacological management of organophosphate poisoning (OPP). Atropine has the potential to cause central toxicity which may complicate the management of this life-threatening condition. A combination of atropine and glycopyrrolate in equivalent dosages titrated to the peripheral muscarinic signs, theoretically reduces the central effect of the anticholinergics by 50% and thereby the risk of central toxicity, while it provides effective control of the peripheral manifestations of OPP. This study reports the clinical morbidity and mortality associated with the management of OP with this anticholinergic combination over a 4-year period, 2003 to 2006, at Tygerberg Academic Hospital (TAH). Two of the 53 patients treated for OPP died, with this mortality lower than that previously reported at TAH. Atropine toxicity was evident in 12 (22.5%) patients and responded to a temporary cessation of the combination infusion. The demographic profile, presenting symptoms, duration of stay and complications encountered were similar to previous reports from TAH. Patients treated with the infusion of a combination of atropine and glycopyrrolate had a lower mortality rate compared with earlier reports from the same unit, but the occurrence of atropine toxicity was unchanged despite the hypothesized theoretical advantage.