Epidermolysis bullosa acquisita occurring in association with systemic lupus erythematosus

A 77-year-old retired male physician with a 6-year history of systemic lupus erythematosus (SLE) developed a mechanobullous eruption, the features of which were clinically and immunopathologically consistent with a diagnosis of 'classical' epidermolysis bullosa acquisita (EBA). As EBA shares immunopathological findings with a number of cases reported as the 'bullous eruption of SLE', the clinical findings commonly recognized as 'classical EBA' may, in patients with SLE, represent a specific subset of the bullous eruption of SLE rather than a separate diagnostic entity. There are few reports in the literature describing classical EBA in patients with SLE. Findings in this patient add further support to the suggestion that EBA occurring in association with SLE, represents a subset of the bullous eruption of SLE, the clinical features of which may be modified by genetic susceptibility or disease activity.     

Epidermolysis bullosa acquisita diagnosed by direct immunoelectron microscopy of the conjunctiva

OBJECTIVE: To describe for the first time the direct immunoelectron microscopic pattern of immune deposits on the conjunctival basement membrane in epidermolysis bullosa acquisita (EBA). DESIGN: Case reports. PARTICIPANTS: Two patients. INTERVENTION: Epidermolysis bullosa acquisita associated with cicatrizing conjunctivitis. MAIN OUTCOME MEASURES: Direct immunofluorescence and direct immunoelectron microscopy without freezing on conjunctival and skin biopsy specimens, indirect immunofluorescence, Western immunoblot analysis. RESULTS: Results of direct immunoelectron microscopic examination of the conjunctiva showed the presence of immune deposits in the anchoring fibril zone, just beneath the lamina densa, in both patients. This finding was the same as the direct immunoelectron microscopic pattern shown in the skin of these patients, which is known to be very specific for EBA. Direct immunofluorescence was positive in the conjunctiva of only one patient. Indirect immunofluorescence and Western immunoblot analysis failed to detect circulating autoantibodies. CONCLUSIONS: Direct immunoelectron microscopy on the conjunctiva is a useful diagnostic tool to differentiate EBA from other related autoimmune mucocutaneous blistering diseases.     

Focal pachypolymicrogyria in three siblings

Low-power bright field photomicrographs often suffer from insufficient sharpness, uneven illumination, and colour hues. Using a film scanner, commercially available and designed for digitizing 35-mm transparencies, we directly scanned microscopic slides that carried dye-labelled and stained sections. The digital images covered a field of up to 24 x 36 mm and revealed excellent sharpness, absolutely even illumination and superior colour reproduction as compared to conventional photomicrographs taken with binoculars, macro lenses, or microscopes. As the method requires neither specialized instrumentation nor expert knowledge of photomicrographic techniques, it reduces costs and saves time. The high-quality digital survey micrographs can easily be used for image processing, image analysis and morphometry. Thus, this new method is valuable not only for pathology, embryology, histochemistry, and the neurosciences, but also for the exchange of low-power micrographs via the internet and for computer media that are increasingly used in medical education.     

Epidermolysis bullosa herpetiformis (Dowling-Meara type) exhibits ultrastructural derangement of tonofilaments and desmosomes

Ultrastructural and immunohistochemical studies of clinically intact skin obtained from three severe neonatal cases of epidermolysis bullosa herpetiformis (Dowling-Meara type) demonstrated disorders in the assembly of keratin intermediate filaments and desmosomes of the keratinocytes. During mitosis, K5- and K14-positive and K1- and K10-negative tonofilaments were disrupted and formed spherical bodies associated with intracytoplasmic desmosomes by invagination of the desmosomes and the adjacent plasma membrane. During the invagination process, destructive changes in the internalized membrane were noted. These were accompanied by gradual loss of reactivity with a monoclonal antibody ZK31, which detected plasma membrane adjacent to the attachment plaques of desmosomes. However, the reactivity of the attachment plaques of the internalized desmosomes for desmoplakins and desmoglein did not decline during the process of internalization. In the suprabasal layers of the epidermis, filamentous substructures and K1 and K10 appeared at the periphery of the spherical bodies. Simultaneously, the desmosomes that were sparsely located in the lower epidermis, increased in number as cell differentiation progressed. Thus, the keratinocytes attained an almost normal appearance with respect to tonofilaments and desmosomes by the time they reached the upper layer of the epidermis. These findings may be relevant to the mechanism responsible for the clinical appearance of the herpetiform blisters in epidermolysis bullosa herpetiformis, which are also characterized by spontaneous involution during childhood or when exposed to high ambient temperatures.     

Fibrodysplasia ossificans progressiva and synovial chondromatosis

Central nervous system vasculitis in Crohn's disease. A 36-years old man was referred to the hospital because of severe headache, vertigo and right sided combined motor-sensory hemiparesis. There was a history of Crohn's disease with an acute exacerbation only two months ago. Magnetic resonance imaging detected a vascular lesion of the left brainstem and serologic investigations revealed circulating immunocomplexes and p-antineutrophil cytoplasmic autoantibodies (p-ANCA). Further investigations care no evidence of arteriosclerotic cerebrovascular disease. These findings therefore suggest that cerebral vasculitis secondary to Crohn's disease was the underlying cause of this focal neurologic deficit.     

Mild cystic fibrosis disease in three Mexican delta-F508/G551S compound heterozygous siblings

We describe three delta-F508/G551S compound heterozygous siblings with a mild CF phenotype, characterized by mild chronic pulmonary disease, pancreatic sufficiency and increased sweat chloride levels. PCR-mediated site-directed mutagenesis detected the delta-F508 mutation on one allele, and the G551S mutation was detected by SSCP and sequence analysis of exon 11. Two previously described sisters who were homozygous for the G551S mutation had a very mild phenotype with normal sweat chloride concentrations. In our patients the mild phenotype resulted from the combined effect of the mild G551S allele with the severe delta-F508 allele.     

Congenital chylothorax in siblings

We describe two cases of congenital chylothorax in siblings with important differences from previously described familial cases. Our findings support the likelihood of an autosomal recessive inheritance in some cases of this condition, rather than X-linked recessive inheritance, which has also been suggested. Autopsy findings from one of these cases and others previously described suggest that the pathophysiological mechanisms involved may be variable.     

Pulmonary and cardiac function in advanced fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by heterotopic ossification in soft tissues. Severe disability results from progressive immobilization of the limbs, jaw, and chest wall. To determine whether cardiac function is altered in this disease, 25 patients ranging in age from 5 to 55 years (disease duration 1-51 years) were studied. History, physical examination, pulmonary functions, electrocardiography, and echocardiography were performed on each patient. Physical examination of the lungs and heart was unrevealing; no right sided ventricular gallops were heard, and no patient was found to have neck vein distention or peripheral edema. The patients had extremely limited chest expansion (1.9 +/- 0.8 inches), suggesting dependence on diaphragmatic breathing. Lung volumes were severely reduced (mean forced vital capacity 44% +/- 14% of predicted), but flow rates were relatively normal. All patients had normal capillary oxygen saturation. Echocardiography was technically difficult, but no abnormalities of left or right ventricular function were seen. Ten (40%) patients had electrocardiographic evidence of right ventricular dysfunction. Compared with patients without such evidence, these patients were older, had significantly longer disease duration, higher hemoglobin, and more impaired pulmonary function. The results of this study suggest that the presence of severely restrictive chest wall disease is associated with a high incidence of right ventricular abnormalities on electrocardiogram. Whether cor pulmonale will eventually occur remains to be determined.     

Oesophageal involvement in epidermolysis bullosa

Epidermolysis bullosa dystrophica causing oesophageal stricture in two males of a family of 4 siblings--2 females and 2 males, and whose parents are not related, is reported. The stricture was treated with repeated dilatations and oral prednisolone on and off with complete success. A brief comment is also made with regards to the pathology and management of this condition.     

Parent ratings of EAS temperaments in twins, full siblings, half siblings, and step siblings.

A twin/family design was used to explore genetic contributions to personality; to evaluate whether twins and nontwins yield different genetic results; and to test for the presence of contrast effects, the tendency of a rater to contrast one sibling with the other, thereby magnifying existing behavioral differences. The sample consisted of 708 adolescent same-sex sibling pairs from 10 to 18 years of age. Pairs included identical (monozygotic; MZ) and fraternal (dizygotic; DZ) twins, and full siblings in nondivorced families; and full, half, and unrelated siblings in stepfamilies. Mothers and fathers rated the temperament of their children on the EAS Temperament Survey (A. H. Buss & R. Plomin, 1984). Model-fitting analyses revealed significant genetic infiuences on each of the four EAS dimensions; however, for some dimensions, heritability estimates were significantly greater for twins than for nontwins. Overall, the data were best described by a sibling interaction model, which indicated significant contrast effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hodgkin's disease in siblings

An incidence survey of Hodgkin's disease in Greater Boston during 1959-1973 detected five sibling pairs under the age of 45. The expected number is 0.7; thus, siblings of young adults with Hodgkin's disease have about a sevenfold excess risk of the disease (P = 0.0008). Eight sibling pairs, not in the incidence series, were also identified. Among all 13 pairs, 12 were sex concordant; the number expected is 6.8 (P = 0.01). The literature includes 46 sibling pairs under 45 of which 30 are sex concordant. The expected number is 23.9 (P = 0.05). Combining the present and the literature series suggests that siblings of the same sex as an affected person have a risk of Hodgkin's disease double that of siblings of the opposite sex. The sex concordance suggests that the excess Hodgkin's disease among siblings of affected persons is due either to inter-personal transmission of an etiologic agent by prolonged or intimate contact or to common-source exposures.     

Catastrophic falls in patients who have fibrodysplasia ossificans progressiva

There have been numerous anecdotal reports of catastrophic falls in patients with fibrodysplasia ossificans progressiva. To determine the incidence of serious morbidity and mortality associated with falls in this patient population, the authors surveyed the 135 patient members of the International Fibrodysplasia Ossificans Progressiva Association and an age and gender matched control group. Eighty-one percent of the fibrodysplasia ossificans progressiva population suffered a fall resulting in injury compared with 44% of the controls. Sixty-seven percent of the falls initiated a painful flareup of fibrodysplasia ossificans progressiva leading to permanent loss of movement in almost all patients. Fifty-four percent of all falls suffered by the fibrodysplasia ossificans progressiva group led to permanent disability compared with 4% of all falls in the control group. Although trauma to the head was a common site of injury in both groups, the injury profile in the fibrodysplasia ossificans progressiva group included traumatic brain injuries, intracranial hemorrhage and death whereas the control group suffered mostly minor soft tissue lacerations. Deficiencies in coordinate gait and protective function likely accounted for the severity of injuries especially to the head in the fibrodysplasia ossificans progressiva population. Precautions are recommended that are intended to minimize the risk of injury without compromising a patient's functional level and independence. These recommendations include limitation of high risk activities, protective head gear, safety improvements in living environments, and augmentation of stabilizing and protective functions.     

Limb swelling in patients who have fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva is a rare heritable disorder of connective tissue characterized by progressive heterotopic ossification of soft tissues and by congenital malformation of the great toes. Limb swelling has also been noted, yet little is known about this complication of fibrodysplasia ossificans progressiva. To determine the prevalence of limb swelling in this condition, the authors reviewed detailed medical records on 74 patients (25 males, 49 females; age range, 1-49 years) who had a documented history of fibrodysplasia ossificans progressiva. The study population included more than 90% of all patients known to have fibrodysplasia ossificans progressiva in the United States. Acute swelling of the limbs occurred in association with flareups of the condition in nearly all cases. Acute swelling in the upper limbs was focal and nodular in contrast to acute swelling in the lower limbs, which was more diffuse. Acute swelling in the upper limbs occurred in all 74 patients whereas acute swelling in the lower limbs occurred in 47 of the 74 patients (64%). Two of the 74 patients who had acute swelling in the lower limbs (4%) had a documented episode of deep vein thrombophlebitis. Chronic swelling in the upper limbs occurred in 9 of the 74 patients (12%) and was not seen before the age of 12 years. Chronic swelling in the lower limbs occurred in 36 of the 74 patients (49%) and was not seen before the age of 9 years. The intense angiogenesis and edema seen on histopathologic evaluation of preosseous fibrodysplasia ossificans progressiva lesions may play a role in the pathogenesis of the limb swelling. The data show an age related prevalence of limb swelling in fibrodysplasia ossificans progressiva and suggest a model for understanding the complex pathways leading to limb swelling in this disorder.