Andrea Gat

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

RIN2 Deficiency Results in Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis: MACS Syndrome

Inherited disorders of elastic tissue represent a complex and heterogeneous group of diseases, characterized often by sagging skin and occasionally by life-threatening visceral complications. In the present study, we report on an autosomal-recessive disorder that we have termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis). The disorder was mapped to chromosome 20p11.21-p11.23, and a homozygous frameshift mutation in RIN2 was found to segregate with the disease phenotype in a large consanguineous kindred. The mutation identified results in decreased expression of RIN2, a ubiquitously expressed protein that interacts with Rab5 and is involved in the regulation of endocytic trafficking. RIN2 deficiency was found to be associated with paucity of dermal microfibrils and deficiency of fibulin-5, which may underlie the abnormal skin phenotype displayed by the patients.

Clinical applications of gamma-detection probes – radioguided surgery

Abstract.Radioguided surgery (RGS) is a surgical technique that enables the surgeon to identify tissue ”marked” by a radionuclide before surgery, based on the tissue characteristics, the radioactive tracer and its carrying molecule, or the affinity of both. Thus, yet another tool has been added to the inspection and palpation traditionally used by the surgeon. Current clinical applications of radioguided surgery are: radioimmunoguided surgery (RIGS) for colon cancer, sentinel-node mapping for malignant melanoma (which has become state-of-the-art), sentinel-node mapping for breast, vulvar and penile cancer, and detection of parathyroid adenoma and bone tumour (such as osteid osteoma). Although the same gamma-detecting probe (GDP) may be used for all these applications, the carrier substance and the radionuclide differ. MoAb and peptides are used for RIGS, sulphur colloid for sentinel-node mapping, iodine-125 for RIGS, technetium-99m for sentinel node, parathyroid and bone. The mode of injection also differs, but there are some common principles of gamma-guided surgery. RIGS enables the surgeon to corroborate tumour existence, find occult metastases, and assess the margins of resection; this may result in a change on the surgical plan. Sentinel lymph-node (SLN) scintigraphy for melanoma guides the surgeon to find the involved lymph nodes for lymph-node dissection. SLN for breast cancer is being investigated with promising results. This procedure has also changed the outlook of lymph-node pathology by giving the pathologist designated tissue samples for more comprehensive examination. Gamma-guided surgery will result in more accurate and less unnecessary surgery, better pathology and, hopefully, in better patient survival.

Clinical and histopathological results following TriPollar™ radiofrequency skin treatments

Abstract Introduction: Skin laxity, wrinkles and cellulite are common aesthetic problems associated with the aging process. These symptoms are due to the weakening and thinning of dermal connective tissue and the enlargement of hypodermal fat cells. The aim of this study was to evaluate the safety and efficacy of the TriPollar RF technology in reducing fat and collagen regeneration. Methods: Twelve healthy patients underwent weekly treatments on different body sites using the TriPollar technology. Treatment areas were photographed and measured and patient satisfaction was monitored. One abdominal patient consented to a series of TriPollar treatments prior to her scheduled abdominoplasty. A controlled histopathology analysis was performed on skin samples taken during the abdominoplasty procedure. Results: Histopatho-logical examination revealed marked differences between treated and non-treated abdominal skin areas. An increase of 49% in dermal thickness, focal thickening of collagen fibers and focal shrinkage of fat cells was shown following TriPollar treatments. Average patient satisfaction indicated clear satisfaction with the clinical results achieved. Conclusion: The TriPollar is a safe and effective non-invasive technology leading to skin tightening and body shaping. Histology results indicate changes at the dermal and fat layers following TriPollar treatments resulting in increased collagen regeneration and stimulated fat metabolism.

CEDNIK syndrome results from loss-of-function mutations in SNAP29.

Background  CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare genodermatosis which was shown 5 years ago in one family to be associated with a loss‐of‐function mutation in SNAP29, encoding a member of the SNARE family of proteins. Decrease in SNAP29 expression was found to result in abnormal lamellar granule maturation leading to aberrant epidermal differentiation and ichthyosis.

Paraneoplastic Subacute Cutaneous Lupus Erythematosus: Report of a Case Associated with Cancer of the Lung

A case of subacute cutaneous lupus erythematosus (SCLE) associated with lung carcinoma is presented. A review of the literature revealed only 5 other cases of SCLE associated with internal malignancy. The tumor in the described case most probably developed before the appearance of the eruption. Cancer chemotherapy was followed by shrinkage of tumor mass and regression of the skin lesions. The sequence of these events corresponds to the definition of paraneoplastic dermatoses.

Peritoneal tuberculosis versus advanced ovarian cancer : A diagnostic dilemma

A 23-year-old married woman was hospitalized because of aggravating abdominal pain and swelling of 3 month’s duration. Her medical history was unremarkable. Gynecologic history included regular menstrual cycles and one term delivery 2 years previously. Physical examination revealed marked abdominal distention, cul-de-sac nodularity, and enlarged tender right adnexa. Abnormal laboratory results included a raised erythrocyte sedimentation rate and an elevated level of CA 125 (460 U/mL). Chest x-ray revealed no abnormalities. Transvaginal ultrasound detected ascites and an enlarged (5 cm diameter) right ovary of variable echodensity. A computed tomography scan revealed ascites, bilateral solid pelvic masses (5 cm diameter), enlarged retroperitoneal lymph nodes, overdistended small bowel loops with thickened walls, and “omental cake.” Ascitic fluid obtained by paracentesis was negative for bacteria, acid-fast bacilli, and malignant cells. Ascitic fluid glucose, lactate dehydrogenase, and protein levels were 46 mg/mL, 351 U/mL, and 7.0 g/dL, respectively. The ascitic white blood cell count was 1500/mm, and the lymphocytic count was 93%. A tuberculin test showed an induration of 13 mm in diameter. Clinical interpretation of these various results was inconclusive and did not facilitate any definite diagnosis. Therefore, explorative laparotomy was elected. At laparotomy, the peritoneal cavity was found to contain 500 mL ascitic fluid. Multiple miliary deposits were scattered over the parietal and visceral peritoneum and extensive adhesions caused conglomerations of omentum, mesentery, bowel loops, and pelvic organs. Multiple biopsies were taken for immediate frozen section evaluation, which revealed epithelioid granulomas suggestive of tuberculosis. Following these results, the uterus and adnexae were left intact. Further postoperative histopathologic evaluation confirmed the diagnosis of tuberculous granulomas containing acid-fast bacilli. The patient was treated by a regimen of isoniazid, ethambutol, and rifampin for 6 months. After therapy, the ascites disappeared and serum CA 125 level was undetectable.

Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP1 gene

Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare hereditary, autosomal dominant, auto‐inflammatory disease caused by mutations in the PSTPIP1 gene, which encodes proline–serine–threonine phosphatase interacting protein 1. The fact that PSTPIP1 is involved in immune regulation provides a rationale for treatment of this rare disease with interleukin (IL)‐1 signalling blocking agents.

A mixed immunoblistering disorder exhibiting features of bullous pemphigoid and pemphigus foliaceus associated with Spirulina algae intake

An 82‐year‐old healthy woman presented with bullae, partly hemorrhagic, on the trunk and extremities ( Fig. 1 ), secreting erosions, and submammary macerations ( Fig. 2 ). The blistering disease developed over a 2‐year period, during which she reported taking no drugs. She did, however, begin using a food supplement containing the blue–green alga Spirulina platensis 1 year before the onset of the eruption.

Efficacy of antibodies against the N-terminal of Pseudomonas aeruginosa flagellin for treating infections in a murine burn wound model.

Background: In an era of increasing drug resistance, immunotherapy is a desirable treatment against Pseudomonas aeruginosa infections. The flagellum, which is an important pseudomonal virulence factor, was targeted for immunotherapy. The aim of the study was to evaluate the efficacy of polyclonal immunotherapy targeted against the N-terminal of flagellin (anti-N′-fla-b) for treating severe P. aeruginosa infection in a murine burn wound model. Methods: Groups of 12 mice were infected (subeschar) with P. aeruginosa strain PA01, and were treated either with systemic anti-N′-fla-b immunoglobulin G (IgG), nonspecific IgG, or imipenem. The control groups included mice with burn alone, mice with untreated infected burn, and mice without burn infected with P. aeruginosa. Three separate regimens were examined: prophylaxis (preinfection), therapeutic (postinfection), and combined. The efficacy of anti-N′-fla-b was evaluated by monitoring the mortality and morbidity (relative weight loss) during a period of 2 weeks. Results: Anti-N′-fla-b IgG immunotherapy significantly decreased the mortality rate of infected burned mice followed by severe P. aeruginosa infection. The mortality rate in the anti-N′-fla-b–treated groups ranged from 0 to 17 percent compared with 58 to 83 percent in nontreated groups infected with 2 to 5 × 106 colony-forming units of P. aeruginosa (p < 0.05). The mortality rate in the anti-N′-fla-b–treated groups was similar to that of groups treated with imipenem. The three tested regimens yielded similar results. Morbidity paralleled survival results. Histopathologic examination revealed an earlier reepithelialization of the infected wound in the anti-N′-fla-b–treated mice compared with untreated mice. Conclusion: Immunotherapy with anti-N′-fla-b IgG, given either as prophylaxis or therapeutically, effectively reduced mortality and morbidity and improved wound healing in a severely P. aeruginosa–infected murine burn model.