Maria A. Barnadas

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of literature.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease with poor prognosis when associated with malignant neoplasm. We report the case of a patient with PNP associated with a CD20+ non‐Hodgkin follicular lymphoma who was treated with Rituximab plus corticosteroids and short courses of cyclosporin. One and a half years after Rituximab therapy, oral ulcerations had cleared and oral methylprednisolone was slowly tapered down without further recurrences. In the course of the disease, the patient developed sepsis due to Listeria monocytogenes and viral infections by human herpes virus 1 and 3. At the end‐stage of the disease she developed a cutaneous infection from Mycobacterium chelonae. The patient died 2 years and 7 months after the onset of PNP. Rituximab may be useful for PNP therapy, but further studies are necessary to confirm this hypothesis.

Detection of Mycobacterium tuberculosis complex DNA by the polymerase chain reaction for rapid diagnosis of cutaneous tuberculosis

Summary We assessed the polymerase chain reaction (PCR) technique to detect Mycobacterium tuberculosis complex DNA In 48 paraffin‐embedded specimens from 32 patients with different variants of cuttineous tuberculosis, and compared the resuts with those of culture. A 123 bp product of the 1S6110 insertion sequence specific of M. tuberculosis complex was amplified and confirmed by digestion with Sall restriction endonuclease. The time required for the procedure was 3 days. Thirty‐seven samples (77.1%) were positive for M. tuberculosis complex DNA. No false positive results were obtained in nine negative controls, Of the 20 specimens tested by PCR and culture, the frequency of positivity was 90% for DNA amplification and 65% for culture. In seven cases of lupus vulgaris, the figures were 100% and 57% respectivety. In the 11 specimens culture negative or not microbiologically tesled and PCR negative, evidence for tuberculous infection was provided hy the correlation of various relative fmd absolute criteria. These results show that PCR amplification of the IS6110 insertion fragment is a rapid and accurate means for the detection of M. tuberculosis complex DNA in paraffin‐embedded skin biopsies from patients with cutaneous tuberculosis, especially in paucibacillary lesions.

Median raphe cyst of the penis with ciliated cells.

Cystic lesions occurring on the ventral surface of the penis have been classified as median raphe cysts of the penis. They are lined by pseudostratified, columnar or stratified squamous cell epithelium, mimicking the epithelial lining of the male urethra. Ciliated cysts of the human skin are unusual. Cystic lesions containing ciliated cells have been noted to occur in the chest, neck, or head, and bronchogenic origin has been the most accepted explanation for its origin. Other reports show the presence of ciliated cysts on the lower extremities, and the mechanism of formation is still a debated question. A case of median raphe cyst of the penis containing ciliated epithelium is presented. The existing literature about these cutaneous lesions is reviewed, including the possible mechanisms believed to be involved in its origin.

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis

Background    No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis.

Systemic capillary leak syndrome

Systemic capillary leak syndrome is a rare, severe disorder with a high mortality rate. It consists of the shift of fluid and proteins from the intravascular to the extravascular compartment with subsequent hypovolemic shock. We describe a 34-year-old-woman who had several episodes of generalized edema that evolved to hypovolemic shock. During the acute phase, laboratory investigations revealed marked hypoproteinemia, leukocytosis, and high levels of hematocrit and hemoglobin. A paraprotein IgG kappa chain was detected. Although different therapeutic trials were used, the patient continued to have similar episodes and she died during an acute episode 2 1/2 years after the first symptom of this disorder. The cause of systemic capillary leak syndrome is unknown. The presence of a paraprotein IgG is frequent in this group of patients.

Enzyme‐linked immunosorbent assay (ELISA) and indirect immunofluorescence testing in a bullous pemphigoid and pemphigoid gestationis

Enzyme‐linked immunosorbent assay (ELISA) is an excellent tool for detection of circulating antibodies against the NC16A portion of BP180 antigen. We compared the sensitivity and specificity of a commercially available BP180‐NC16a domain ELISA with that of an indirect immunofluorescence (IIF) testing in the evaluation of bullous pemphigoid (BP) and pemphigoid gestationis (PG), and analyzed the relationship between ELISA results and the presence of IgG deposition, in an epidermal or combined pattern, on direct immunofluorescence (DIF) testing of salt‐split skin. ELISA was performed on serum from 28 patients (24 BP, 4 PG) and 50 controls. IIF testing was performed on serum from 27 patients and 98 controls. For the group of 28 patients with BP or PG, ELISA had a sensitivity of 93% and specificity of 96% (P < 0.001), while sensitivity was 74% and specificity 96% (P < 0.001) for IIF testing. In these patients, ELISA has a higher sensitivity than IIF testing, but similar specificity. Evaluation of controls who had IgG deposition on the dermal side of salt‐split skin on DIF testing showed specificity for the ELISA of 100% (all four cases negative) and 80% for IIF testing (one of five positive). Positive ELISA correlated with a diagnosis of BP or PG only in patients who had IgG at the basement membrane zone (BMZ) by DIF testing. Overall, ELISA appears to have greater sensitivity and specificity for BP or PG than does IIF testing.

Mycobacterium abscessus infection secondary to mesotherapy

First developed in France in 1952, mesotherapy consists of injecting drugs or other substances into intradermal or subcutaneous tissue for use in medical and cosmetic treatments. Its use in aesthetic medicine has increased considerably in recent years. We report two cases of Mycobacterium abscessus infection secondary to mesotherapy. Patient 1 was a 54-year-old woman, who presented with a 3-week history of a hard, erythematous plaque, 50 · 30 mm in size, on the right buttock (Fig. 1). She had been undergoing weekly mesotherapy for weight loss for 8 months, using an unknown substance administered by a private practitioner. A biopsy was taken. Histopathology showed an acute and chronic inflammatory infiltrate with giant cells involving the upper and lower dermis and fat (Fig. 2). Periodic-acid–Schiff stain was negative. A second punch biopsy was taken, which showed acid–alcohol-resistant bacilli on Ziehl–Neelsen staining, but mycobacteriological culture was negative. Treatment with clarithromycin 500 mg twice daily and ciprofloxacin 500 mg twice daily was given for 4 months, which resulted in complete healing. Patient 2 was a 31-year-old woman, who presented with a 3-week history of multiple painful erythematous nodules, 5–25 mm in size, on the abdomen, thighs and buttocks. The patient had been undergoing mesotherapy for weight loss in these areas, administered by the same practitioner who had treated patient 1. A biopsy was taken, which showed an acute neutrophilic infiltrate in deep reticular dermis. Ziehl–Neelsen staining of a second punch biopsy was negative, but the mycobacteriological culture was positive for M. abscessus. This patient was treated with clarithromycin and minocycline, but the latter was replaced by sulfamethoxazole 800 mg three times daily and trimethoprim 160 mg three times daily based on antibiogram testing. The patient completed 6 months; treatment. Atrophic hyperpigmented scars remained at injection sites after treatment, but no recurrence was observed at the 6-month follow-up. We believe that the first patient had a M. abscessus infection because Ziehl–Neelsen staining was positive and both patients underwent mesotherapy at the same clinic. In an epidemiological study, the Catalan Health Service detected an outbreak of cutaneous M. abscessus infection in 13 patients, including both of the patients reported here, who had undergone mesotherapy at the same clinic over the same period. All cases presented cutaneous nodules and ⁄ or abscesses, and M. abscessus was cultured in four cases, including one of our two patients. Several complications and adverse effects of mesotherapy have been described in the literature. Soft-tissue infection by M. abscessus is typically caused by infected material, nonsterile surgical procedures, injections and foreign body implantation. M. abscessus is frequently detected in Figure 2 Patient 1. Acute and chronic inflammatory infiltrate involving the upper and lower dermis and fat. Figure 1 Patient 1. Clinical appearance of the lesion. Correspondence

Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres

Summary Acquired cutis laxa (ACL) is an uncommon elastolytic disorder of unknown aetiology. In rare instances. ACL has been reported in association with autoimmune diseases and dermal deposit of immunoglobulins, suggesting that destruction of elastic tissue may be immunologically mediated. We report a 35‐year‐old man with generalized acquired cutis laxa (GACL) associated with a persistent papular erythematous eruption that histopathologically showed some resemblance to dermatitis herpetiformis. A marked reduction and degeneration of dermal elastic fibres was noted in biopsies from loose‐hanging skin. Direct immunofluorescence from non‐inflammatory loose skin revealed granular immunoglobulin A (IgA) deposits at the basement membrane zone and fibrillar IgA deposits in the dermal papillae. IgA deposits were also observed on the elastic fibres of the reticular dermis. Electron microscopy of skin from the submammary fold revealed fragmented elastic fibres, partial absence of peripheral microfibrils and abundant neutrophils, some of which were degranulated and adjacent to elastic fibres. Immunoelectron microscopy of an erythematous papule revealed IgA deposits around dermal elastic fibres. Antigliadin, antireticulin and antiendomysium antibodies were present. Jejunal biopsies showed a gluten‐sensitive enteropathy. A possible IgA‐mediated immune mechanism for the development of GACL in our patient is suggested.

Sunscreen and risk of osteoporosis in the elderly: a two-year follow-up.

Background: It has been suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency, which in turn may lead to secondary hyperparathyroidism, loss of cortical bone and, ultimately, osteoporotic fractures. Objective: To investigate whether sunscreen SPF15 may lead to loss of bone mass. Methods: We followed 10 sunscreen users and 18 controls over 2 years, including two summers, two winters and a basal period (winter). Bone mass was evaluated each season with dual x-ray absorptiometry. Results: During follow-up, mild fluctuations in bone mass could be seen at Ward’s site in both groups, without a definitive pattern. At the final visit, no significant loss of bone mass was observed in sunscreen users or in the control group. We did not observe any significant differences between groups throughout the study. Conclusion: Although the study samples in this work are small, and a slight variation in bone mass may not be detected, in a clinical setting, sunscreen SPF15 protection does not seem to increase the risk of osteoporosis.