ABSTRACT
We aimed to investigate the epidemiological determinants, clinical features, and genetic pattern of FOP in our country by evaluating the entire population of patients identified according to a combination of methods. To achieve this, 24 individuals were confirmed as FOP cases, 17 of whom were alive at the end of 2011 (point prevalence=0.36 × 10(-6)). The gender distribution (male/female ratio=13/11) and the concurrent range of ages (from 4 to 53 years; mean ± SD: 30.2 ± 13.8) are in agreement with similar reports. Twenty-one (87.5%) had characteristic congenital malformations of the big toe, and short thumbs were found in 65.2% of cases. In addition, other skeletal malformations such us fusion of the posterior elements of the cervical spine (89.0%), knee osteochondromas (71%), scoliosis (54.5%), and short and broad femoral neck (52.6%) were observed. All had developed mature ossicles of heterotopic bone in typical anatomic and temporal patterns, ranging in number from 1 to 17 (9.5 ± 3.9). Age at appearance of first ossifying lesion varied from 3 months to 15 years. Mean age at diagnosis was 7.3 ± 5.1 years and the average delay in reaching the correct diagnosis after the onset of heterotopic ossification was 2.7 years (range=0-12 years). Biopsy of the pre-osseous lesions was performed in 11 of 20 (55.0%), providing no useful information for the diagnosis of FOP. Seven of 18 (38.9%) reported some hearing loss, and 5 (27.8%) experienced diffuse thinning of the hair or were bald. No patient had relatives with a typical FOP clinical picture. Fourteen of the 16 cases which were genetically investigated displayed the single heterozygous mutation c.617G>A in exon 4 of the ACVR1 gene. One of the two patients who did not present with the canonical ACVR1 mutation showed a heterozygous mutation c.774G>C in exon 5 leading to the substitution of Arginine 258 with a serine. The other patient had a heterozygous c.774G>T substitution in exon 5 leading to the same amino acid change (p.Arg258Ser). These two patients had only nonspecific abnormalities of the great toe, lacked the typical anatomic and developmental pattern of heterotopic ossification, and shared a trend toward uncommon clinical features. These results provide new insight on the epidemiological and clinical traits of FOP, reinforcing the notion of its worldwide homogeneity. The molecular characterization of ACVR1 sequence variation will contribute to the understanding of the genetic profile of this devastating disease in different geographical areas.
Subject(s)
Myositis Ossificans , Activin Receptors, Type I/genetics , Adolescent , Adult , Child , Child, Preschool , Exons , Female , Heterozygote , Humans , Male , Middle Aged , Mutation , Myositis Ossificans/epidemiology , Myositis Ossificans/genetics , Myositis Ossificans/pathology , Spain/epidemiology , Young AdultABSTRACT
OBJECTIVES: Our objective was to evaluate the efficacy and tolerability of bosentan in patients with systemic sclerosis (SSc) who develop ulcers and healed ulcers. We also wanted to analyse the effect of bosentan on other skin and general outcome measurements. METHODS: In the present prospective, observational, non-controlled study, we followed all patients with SSc who started treatment with bosentan for ischaemic ulcers and healed ulcers from January 2003 to June 2006 in our centre. We recorded skin and general outcome measurements at baseline and at 6 months. RESULTS: Fifteen patients were included. After a median follow-up of 24.7 months (range: 4-36), there was a significant decrease in the number of ulcers. A trend towards efficacy was seen in the number of healed ulcers and in the severity of ulcers. No significant effect was seen in other skin and general outcome measurements. Toxicity related to bosentan included mild transitory events and one toxic hepatitis. CONCLUSION: Bosentan may be a safe long-term alternative for treating the recurrence of skin ulcers and healed ulcers in SSc patients.
Subject(s)
Scleroderma, Systemic/drug therapy , Skin Ulcer/drug therapy , Sulfonamides/therapeutic use , Adolescent , Adult , Aged , Bosentan , Child , Endothelin Receptor Antagonists , Female , Humans , Male , Middle Aged , Prospective Studies , Scleroderma, Systemic/complications , Severity of Illness Index , Skin Ulcer/etiology , Sulfonamides/adverse effects , Treatment OutcomeSubject(s)
Rheumatic Diseases/diagnosis , Abnormalities, Multiple/diagnosis , Child , Humans , Male , Rheumatic Diseases/drug therapy , SyndromeSubject(s)
Arthritis, Juvenile/therapy , Anti-Inflammatory Agents/therapeutic use , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/psychology , Arthritis, Juvenile/rehabilitation , Aspirin/therapeutic use , Child , Humans , Immunosuppressive Agents/therapeutic use , Physical Therapy ModalitiesABSTRACT
A selective IgA deficiency (SD IgA) appears in a 0.15% of the population, being more frequent in autoimmune diseases. We present here eight patients presenting this association who were diagnosed at the Rheumatology Department during a period of eight years. Five patients suffered Juvenile Chronic Arthritis (JCA), two patients Rheumatoid Arthritis (RA) and one Systemic Lupus Erythematous (SLE). There were to cases of familiar deficiency. There was not a relationship between SD IgA and treatments used. There is an important association between SD IgA and JCA (4.27% prevalence). In the other two conditions, however, the association could be casual.
