Increased Morbidity and Mortality of Scleroderma in African Americans Compared to Non-African Americans.

OBJECTIVE: African Americans with scleroderma have more severe disease and higher mortality than non-African Americans. Differences in rates of diffuse disease, autoantibody status, or socioeconomic status have not completely explained this phenomenon. Our study evaluates these risks at our site. METHODS: A retrospective study comparing African American and non-African American patients with scleroderma seen from 2008 to 2016 was performed. Groups were matched by sex, age at first visit, date of first visit, disease duration at first visit, and limited versus diffuse cutaneous disease. Demographic, serologic, and clinical features were compared. Mortality risks were assessed by a Cox proportional hazards model with covariates of race, marital status, education, employment, insurance, and imputed household income. RESULTS: African Americans comprised 202 of 402 patients. They demonstrated reduced forced vital capacity and diffusing capacity for carbon monoxide, more severe lung fibrosis, a higher prevalence of pulmonary hypertension, and more severe cardiac involvement. The autoantibody profile statistically differed between the 2 groups. Death during follow-up was 21% in African Americans versus 11% in non-African Americans (P = 0.005). African American race demonstrated an unadjusted hazard ratio for death during follow-up of 2.061 (P = 0.006) that declined with adjustment for socioeconomic covariates to 1.256 (P = 0.633). The only significant covariate was median income in tens of thousands of dollars by zip code (hazard ratio 0.845; P = 0.033). CONCLUSION: African American patients with scleroderma have more severe pulmonary disease and higher unadjusted mortality than matched non-African Americans. Following adjustment for socioeconomic factors, African American race was not a significant risk factor for mortality; however, independent of race, a lower median household income predicted increased mortality.

A novel mutation in TRPV3 gene causes atypical familial Olmsted syndrome.

Olmsted syndrome (OS) is a rare keratinization disorder, typically characterized by two primary diagnostic hallmarks--mutilating palmoplanter and periorificial keratoderma. However, there's a growing body of literature reporting on the phenotypic diversity of OS, including the absence of aforementioned hallmarks and the presence of some unusual clinical features. Here we presented an atypical familial case of OS that could be confused with Huriez syndrome due to the presence of a scleodactyly-like appearance and tapered fingers in the proband. We ruled out this possibility and made a definitive diagnosis of OS based on clinical features and a genetic assay. Recently, mutations in TRPV3 associated with autosomal dominant or recessive OS continued to be reported, thus conducing to clarifying the underlying relationship between the genotype and phenotype of OS. So we further explored the genotype-phenotype correlation by integrating functionl assays with in silico predictions. Our research not only redefined the phenotypic spectrum of OS, but also provided concrete molecular insights into how mutations in a single gene can lead to significant differences in the severity of this rare disease.

Comparison of outcomes in adults with pediatric-onset morphea and those with adult-onset morphea: a cross-sectional study from the morphea in adults and children cohort.

OBJECTIVE: Few studies have examined outcomes in adults with pediatric-onset morphea. The objective of the present study was to compare clinical outcomes and health-related quality of life (HRQOL) in adults with onset of morphea in childhood to those in patients with adult onset of morphea. METHODS: Participants in the study were drawn from the Morphea in Adults and Children cohort and included 68 adults with pediatric-onset morphea and 234 patients with adult-onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical examination findings, and HRQOL questionnaires. RESULTS: Adults with pediatric-onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric-onset disease were less likely to have active disease. Among patients with active disease, those with pediatric-onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric-onset disease had higher severity of disease damage when measured by the physician's global assessment of damage, but had similar levels of disease damage when measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric-onset disease had more favorable HRQOL scores for all measures, all of which were statistically significantly different from those in patients with adult-onset morphea. CONCLUSION: Adults with pediatric-onset morphea differ from patients with adult-onset disease with respect to disease subtype, severity of disease activity and damage, and levels of HRQOL.

Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature.

Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-2.2), renal (OR, 1.6; 95% CI, 1.2-2.1), digital ischemia (OR, 1.5; 95% CI, 1.4-2.2), muscle (OR, 1.7; 95% CI, 1.3-2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1-9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4-2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0-1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings.

Frequency of antinuclear antibodies in mestizo Mexican children with morphea.

Morphea is a disease that affects connective tissue and microvessels. Its pathogenesis is unknown, but several autoimmune factors participate. Our objective was to determine the frequency of antinuclear antibodies (ANAs) in pediatric patients with morphea and to establish their relation with the clinical variants and disease activity. A cross-sectional study was carried out from January 1999 to January 2008 in patients with morphea seen at the Instituto Dermatologico de Jalisco. ANAs were determined through an indirect immunoflourescent method, and the immunospecificity was done with a double immunodiffusion technique in agarose gel. A total of 34 children were included in the study, 74% of the female gender. Plaque morphea was the most common variant, present in 44% of the cases, followed by linear morphea in 38%, and generalized morphea in 18%. ANAs were positive in 29%, with homogenous immunoflourescense as the most frequent pattern (70%). Of the ANA-positive patients, 83% had generalized morphea, and in 70% of the cases the disease were considered as active. The frequency of ANA-positive children with morphea was 29%, and seems to be related to more extensive disease. No previous studies exist on this topic in the mestizo Mexican population.

Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland.

OBJECTIVE: Childhood scleroderma encompasses a rare, poorly understood spectrum of conditions. Our aim was to ascertain the incidence of childhood scleroderma in its different forms in the UK and Ireland, and to describe the age, sex, and ethnicity of the cases. METHODS: The members of 5 specialist medical associations including pediatricians, dermatologists, and rheumatologists were asked to report all cases of abnormal skin thickening suspected to be localized (including linear) scleroderma or systemic sclerosis (SSc) in children <16 years of age first seen between July 2005 and July 2007. RESULTS: We received notification of 185 potential cases, and 94 valid cases were confirmed: 87 (93%) with localized scleroderma and 7 (7%) with SSc. This gave an incidence rate per million children per year of 3.4 (95% confidence interval [95% CI] 2.7-4.1) for localized scleroderma, including an incidence rate of 2.5 (95% CI 1.8-3.1) for linear scleroderma, and 0.27 (95% CI 0.1-0.5) for SSc. Of the 87 localized cases, 62 (71%) had linear disease. Of localized disease cases, 55 (63%) were female, 71 (82%) were classified as white British, and the patients' mean age when first seen in secondary care was 10.4 years. Of the 7 SSc cases, all were female, 6 (86%) were white British, and the mean age when first seen was 12.1 years. The median delay between onset and being first seen was 13.1 months for localized scleroderma and 7.2 months for SSc. CONCLUSION: These data provide additional estimates of the incidence of this rare disorder and its subforms.

Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions.

OBJECTIVE: In the era of genome-wide association studies, familial risks are used to estimate disease heritability and the likelihood of candidate-gene identification. This study was undertaken to estimate associations of rheumatoid arthritis (RA) with any of 33 autoimmune diseases and related conditions among parents and offspring, singleton siblings, twins, and spouses. METHODS: The Multigeneration Register in Sweden was used as a reliable source of information on Swedish families throughout the last century. Data on autoimmune diseases in individual family members were obtained through linkage to the Hospital Discharge Register. The standardized incidence ratio (SIR) was calculated as a measure of the relative risk of RA in family members of patients with RA or any of 33 other autoimmune diseases or related conditions, as compared with the relative risk of RA in those lacking an affected family member. RESULTS: Among a total of 447,704 patients, 47,361 were diagnosed as having RA. The SIRs for RA were 3.02 in offspring of affected parents, 4.64 in siblings, 9.31 in multiplex families, 6.48 in twins, and 1.17 in spouses. Significant associations with the familial risk of RA in offspring according to parental proband were observed for ankylosing spondylitis (SIR 2.96), localized scleroderma (SIR 2.40), Sjögren's syndrome (SIR 2.25), systemic lupus erythematosus (SIR 2.13), systemic sclerosis (SIR 1.65), Hashimoto thyroiditis/hypothyroidism (SIR 1.54), pernicious anemia (SIR 1.53), sarcoidosis (SIR 1.40), psoriasis (SIR 1.36), Wegener's granulomatosis (SIR 1.34), and asthma or polymyalgia rheumatica (SIR 1.32). CONCLUSION: This is the first study to compare the familial risks of RA in relation to a large number of autoimmune diseases and related conditions using data from a single population. The high discordant familial risks in this population suggest that there is extensive genetic sharing between RA and the associated diseases.

UVA1 phototherapy is effective in darker skin: a review of 101 patients of Fitzpatrick skin types I-V.

BACKGROUND: Studies suggest ultraviolet (UV) A1 phototherapy is efficacious and safe in treating a variety of skin disorders. However, most reports evaluating the benefits of UVA1 phototherapy have been from Europe, focusing on a predominantly Caucasian population. Darker skin types have been evaluated only sparingly; none the less, it is widely held that these patients respond poorly to UVA1 phototherapy due to increased pigmentation. OBJECTIVES: We aim to compare efficacy (clinical improvement scores) of UVA1 phototherapy among Fitzpatrick skin types. METHODS: A retrospective analysis of 101 patients receiving UVA1 treatment at the University of Texas Southwestern Medical Center in Dallas, TX was performed. Data on Fitzpatrick skin type and cumulative UVA1 doses were collected. Clinical improvement scores based on body surface area, erythema, induration, sclerosis, pigmentation, and symptoms of pain or pruritus were obtained. RESULTS: In the population studied, with morphoea and scleroderma being the most frequent diagnoses, improvement scores from UVA1 phototherapy and mean cumulative UVA1 doses were not significantly different among the Fitzpatrick skin types evaluated. Furthermore, little or no correlation was found between improvement score and skin type. CONCLUSIONS: Data indicate skin pigmentation as graded by Fitzpatrick skin type does not significantly influence the efficacy of UVA1 phototherapy. Thus, UVA1 should be considered as a therapeutic option in more darkly pigmented patients.

Pediatric morphea (localized scleroderma): review of 136 patients.

BACKGROUND: Morphea is an autoimmune inflammatory sclerosing disorder that may cause permanent functional disability and disfigurement. OBJECTIVES: We sought to determine the clinical features of morphea in a large pediatric cohort. METHODS: We conducted a retrospective chart review of 136 pediatric patients with morphea from one center, 1989 to 2006. RESULTS: Most children showed linear morphea, with a disproportionately high number of Caucasian and female patients. Two patients with rapidly progressing generalized or extensive linear morphea and arthralgias developed restrictive pulmonary disease. Initial oral corticosteroid treatment and long-term methotrexate administration stabilized and/or led to disease improvement in most patients with aggressive disease. LIMITATIONS: Retrospective analysis, relatively small sample size, and risk of a selected referral population to the single site are limitations. CONCLUSIONS: These data suggest an increased prevalence of morphea in Caucasian girls, and support methotrexate as treatment for problematic forms. Visceral manifestations rarely occur; the presence of progressive problematic cutaneous disease and arthralgias should trigger closer patient monitoring.

[Diabetic hand syndrome in juvenile diabetes].

Patients with Type I diabetes may develop a scleroderma-like syndrome, including limitation of joint mobility. This syndrome, cherioarthropathy, is considered a complication of diabetes, but its cause is unknown. We examined 30 Jewish and 13 Arab patients in our juvenile diabetes clinic for skin and joint involvement. Signs of cherioarthropathy in both hands were found in 13 children (30.2%); all had skin changes and 6 (13.5%) also had articular involvement of the hands. There was no correlation between the presence of cherioarthropathy and the patient's age or the duration of diabetes. The syndrome was significantly more frequent among Arabs (8/15, 61.5%) than Jewish children (5/30, 16.6%), p less than 0.01. There was a indirect correlation between incidence of cherioarthropathy and adequacy of glycemic control, but no difference in glycemic control between Arab and Jewish children. This may indicate a genetic factor in the development of cherioarthropathy in juvenile diabetes.