The course of pregnancy and childbirth in three mothers with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive skin disease caused by mutations in the type VII collagen gene (COL7A1), resulting in detachment of the entire epidermis due to loss or hypoplasticity of the anchoring fibrils that normally secure the basement membrane to the underlying dermis. Trauma-induced blistering is often complicated by chronic erosions and scarring. From that perspective, pregnancy in RDEB might be considered an indication for elective caesarean section in a bid to minimize perineal blistering. To date, only four cases of pregnancy and delivery in patients with RDEB have been reported. CASES: We report three more women, each with RDEB-generalized other (RDEB-GO), all of whom had successful vaginal deliveries without major cutaneous or mucosal complications. One woman also had a second child, by vaginal delivery, indicating a lack of vaginal stenosis after the first birth. CONCLUSIONS: These cases show that RDEB-GO is not an absolute primary indication for elective caesarean section and that, perhaps surprisingly, genital/perineal blistering and scarring are not inevitable consequences of childbirth. Moreover, breastfeeding is also feasible in women with RDEB-GO.

Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course.

Thymoma-associated multi-organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft-versus-host (GVH)-like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin-infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma-associated multi-organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma-associated multi-organ autoimmunity. Histopathological findings of thymoma-associated multi-organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (T(regs)) is reduced in cutaneous lesions and CD8+ cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma-associated multi-organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4+ cells in patients with thymoma-associated multi-organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin-infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma-associated multi-organ autoimmunity might be induced by self-reactive cytotoxic T lymphocytes under the diminished suppressive capacity of T(regs).

A case of generalized acanthosis nigricans with positive lupus erythematosus-related autoantibodies and antimicrosomal antibody: autoimmune acanthosis nigricans?

Acanthosis nigricans (AN) is a hyperpigmented keratotic skin lesion known to be associated with malignant disease and endocrinopathy. We report a very rare case of generalized AN with Sjögren's syndrome- and systemic lupus erythematosus-like features but without type B insulin resistance. Neither internal malignancy nor other endocrinological disorders, including glucose intolerance, were detected during a 10-year clinical course with benign diffuse papillomatosis extending from the mucosa of the larynx to the esophagogastric junction. The case was complicated with chronic thyroiditis and interstitial pneumonia, which were not treated with any medication. AN skin lesions and mucosal papillomatosis regressed with oral cyclosporine A, accompanied by the lowering of autoantibody titers. This is the first report of generalized AN involving an area from the mucosa of the larynx to the esophagogastric junction accompanied by autoimmune manifestations which responded to systemic immunosuppressive therapy.

Oral steroid improves bullous pemphigoid-like clinical manifestations in non-Herlitz junctional epidermolysis bullosa with COL17A1 mutation.

Non-Herlitz junctional epidermolysis bullosa (JEB-nH), a nonlethal variant of junctional epidermolysis bullosa (JEB), is an autosomal recessive disorder characterized by separation of the dermal-epidermal junction. JEB-nH is caused by mutations in several genes and lack of the COL17A1 gene product may lead to skin fragility. A 41-year-old Japanese man with JEB-nH, featuring mutations in the gene encoding type XVII collagen, presented with great blisters over his entire body accompanied by severe itching and eosinophilia usually observed in bullous pemphigoid (BP). To our knowledge, our patient is the first with JEB-nH to be treated successfully with an oral steroid to control his skin affliction, symptoms and eosinophilia. This suggests that in the case of JEB-nH with eosinophilia caused by some secondary immune activation, oral steroids may constitute an alternate therapy to improve aggravated skin conditions and severe itching, both of which tend to show resistance to usual dermatological treatments.

Clarithromycin-resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Japan.

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin is mostly due to the point mutations in the 23S rRNA. In Japan, however, the frequency of these mutations has not been fully investigated. Furthermore, no study has used gastric biopsy specimens to detect these point mutations. METHODS: The frequency of primary clarithromycin-resistant H. pylori was examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Eighty-two strains (42 isolated from patients with gastric cancer and 40 isolated from patients with chronic gastritis) were examined. Two biopsy specimens obtained from patients in whom eradication therapy including clarithromycin had failed were also studied. RESULTS: Either A2143G or A2144G point mutation was detected in 90% of clarithromycin-resistant H. pylori strains. Eight out of 82 strains (9.8%) had either A2143G or A2144G point mutation. Only one out of 42 strains in patients with gastric cancer had A2143G mutation, whereas five strains had A2144G and two had A2143G mutations in 40 strains isolated from control subjects. The proportion was significantly lower in patients with early gastric cancer (P < 0.05). This PCR-RFLP was also applicable for DNA samples extracted from biopsy specimens and infection of clarithromycin-resistant H. pylori was observed. CONCLUSION: The results suggest that the point mutation in the 23S rRNA gene is commonly seen in clarithromycin-resistant H. pylori and it contributes to the treatment failure in Japan. The PCR-RFLP system is a sensitive method by which to diagnose H. pylori infection as well as a simple method for detecting clarithromycin resistance without bacterial culture.

A marked decrease in bispectral index with elevation of suppression ratio by cervical haematoma reducing cerebral perfusion pressure.

A 77-year-old man with a ruptured abdominal aortic aneurysm undergoing aneurysmectomy were anaesthetised with ketamine under bispectral index (BIS) monitoring, which is a clinical EEG monitor for measurement of depth of anaesthesia/sedation. First marked BIS reduction with elevation of suppression ratio (SR) was observed following severe hypotension by deflation of the aortic occlusion balloon. The re-inflation and rapid blood transfusion improved haemodyanamics and BIS and SR. At second marked BIS reduction with SR elevation, a heavy cervical swelling due to a massive subcutaneous haematoma around the previously mis-punctured right carotid artery extending throughout the whole neck was observed without hypotension. Cervical relief incision improved the BIS and SR. The present case suggests that BIS monitor may be a simple and convenient monitor for cerebral ischaemia detection.

Photodynamic therapy may be useful in debulking cutaneous lymphoma prior to radiotherapy.

Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (5-ALA) is a promising new treatment for superficial malignant nonmelanoma tumours, including cutaneous malignant lymphoma. Here, we report a case of cutaneous anaplastic large cell lymphoma effectively treated by PDT with topical 5-ALA in combination with radiotherapy.