International Pemphigus Pemphigoid Foundation

Effektivität und Sicherheit von Rituximab beim Pemphigus: Ergebnisse aus dem Deutschen Register für Autoimmunerkrankungen

Cristo Rey Intern — Sat, 15 Jun 2013 12:00:23 +0000

Klinik für Dermatologie, Allergologie und Venerologie, Universität Lübeck, Deutschland Klinik für Dermatologie und Allergologie, Philipps-Universität Marburg, Deutschland Klinik und Poliklinik für Dermatologie und Venerologie, Universität Köln, Deutschland Klinik für Dermatologie, Technische Universität Dresden, Deutschland Abteilung Rheumatologie, LMU München, Deutschland Abteilung Hämatologie und Onkologie, Siloah Krankenhaus, Hannover, Deutschland United BioSource Corporation, Lörrach, Deutschland Charité Centrum 12 und 14, Charité Universitätsklinikum, und Deutsches Rheuma-Forschungszentrum Berlin, Deutschland Zentrum für Entzündungsmedizin, Universität Lübeck, Deutschland. Journal der Deutschen Dermatologischen Gesellschaft

Schlüsselwörter

Autoantikörper
bullöse Autoimmundermatosen
Pemphigus vulgaris
Register

Zusammenfassung

Hintergrund: Rituxmab hat sich in kleinen Fallserien bei Patienten mit schwerem und/oder refraktärem Pemphigus als effektiv erwiesen. Bislang liegt jedoch keine systematische Untersuchung vor, die diese Beobachtung bestätigen könnte. Das Ziel dieser Studie war es, die Effektivität und Sicherheit von Rituxmab beim therapierefraktären Pemphigus anhand eines Registers systematisch zu ermitteln.Patienten und Methoden: Multizentrische, retrospektive Beobachtungsstudie an 36 Patienten mit schwerem Pemphigus vulgaris (n = 33) und Pemphigus foliaceus (n = 3), die vor dem 31. Sugust 2008 mit Rituxmab behandelt und zwischen Dezember2008 und Juni 2009 in ein nationales Beobachtungsregister eingeschlossen wurden.

Ergebnisse: Innerhalb einer durchschnittlichen Beobachtungsdauer von 11 (1-37) Monaten zeigten 21 (58%) Pemphiguspatienten ein komplettes, 13 (36%) ein partielles und 2 (6%) kein Ansprechen auf die Rituximab-Behandlung. Parallel hierzu kam es zur durchschnittlichen Verbesserung des subjektiven Wohlbefindens auf der visuellen Analogskala mit 34 Punkten (20-60) vor Behandlungsbeginn und 75 (40-95) bei der letzten Kontrollvisite. Bei 4 (11%) Patienten wurden schwerwiegende Nebenwirkungen beobachtet, u.a. eine schwere Infektion (3%). Schlussfolgerungen: Die systematischen Register erhobenen Daten weisen darauf hin, dass Rituxmab eine effektive und relativ sichere adjuvante Behandlungsoption für den refraktären Pemphigus ist. Kontrollierte prospektive Studien sind notwendig, um genauere Kenntnisse über die Effektivität und Sicherheit dieses Medikamentes zu gewinnen.

Summary:

Background: Rituxmab has been reported to be effective in various small case series of patients with severe and/or refractory pemphigus. However, nosystematic evaluation is available to corroborate this observation. The aim of this study was to systematically determine efficacy and safety of rituxmab in treatment-resistent pemphigus.

JDDG: Journal der Deutschen Dermatologischen Gesellschaft

Pemphigus Subaigu Malin à Bulles Extensives

Cristo Rey Intern — Tue, 11 Jun 2013 12:00:10 +0000

Variété de pemphigus vulgaire se caractérisant par la présence de bulles qui finissent par confluer (se rejoindre) et se rompre, créant ainsi de vastes surfaces laissant la peau à vif qui suinte et qui devient très douloureuse.

Généralités

Le pemphigus vulgaire est une variété de pemphigus vrai (groupe des maladies cutanées se caractérisant par l’importance des bulles et l’évolution péjorative entre autres) qui survient à l’âge moyen de la vie et qui se caractérise par l’apparition de bulles de taille plus ou moins importantes, se remplissant d’un liquide de coloration jaune citrin, indolore, sur l’ensemble du corps avec une prédominance aux plis et sur les muqueuses (couche de cellules recouvrant l’intérieur des organes creux en contact avec l’air) essentiellement celles de la bouche.

Historique

Le français Brocq, en 1919, a étudié cette dermatose (maladie de peau) grave.

Évolution

Étant donné la gravité de l’atteinte générale survenant au cours de cette pathologie, l’évolution est souvent péjorative en quelques semaines.

Vulgaris Medical

Pemphigus Vulgaris Activity Score and Assessment of Convergent Validity.

Cristo Rey Intern — Fri, 07 Jun 2013 12:00:54 +0000

Pemphigus is a rare autoimmune blistering disease with different phenotypes. The evaluation of therapeutic interventions requires a reliable, valid and feasible to use measurement. However, there is no gold standard to measure the disease activity in clinical trials. In this study we aimed to introduce the pemphigus vulgaris activity score (PVAS) measurement and to assess the convergent validity with the experts’ opinion of disease activity. In PVAS scoring, the distribution of pemphigus vulgaris antigen expression in different anatomical regions is taking in to account with special consideration of the healing process. PVAS is a 0-18 scale, based on the extent of mucocutaneous involvement, type of lesion and the presence of Nikolsky’s sign. The sum of the scores of total number of lesions, number of different anatomic regions involvement and Nikolsky’s sign is weighted by the type of lesion. In the present study, PVAS was assessed in 50 patients diagnosed with pemphigus vulgaris by one dermatologist. Independently, five blinded experts scored all the patients through physician’s global assessment (PGA). The convergent validity with experts’ opinion was assessed. The Spearman coefficient of correlation showed the acceptable value of 0.751 (95%CI: 0.534- 0.876). PVAS is a valid, objective and simple-to-use scoring measurement. It showed a good correlation with PGA of pemphigus disease activity in Iranian patients with pemphigus vulgaris.

From: Acta medica Iranica

Oral Inflammation in Small Animals

Cristo Rey Intern — Mon, 03 Jun 2013 12:00:56 +0000

The oral cavity can be affected by a wide variety of disorders characterized by inflammation of the gingiva and/or oral mucosa. In dogs and cats, differential diagnoses for generalized oral inflammatory disorders include plaque-reactive mucositis, chronic gingivostomatitis, eosinophilic granuloma complex, pemphigus and pemphigoid disorders, erythema multiforme, and systemic lupus erythematosus. In addition, endodontic or periodontal abscesses, infectious conditions, reactive lesions, and neoplastic conditions may initially present with localized or generalized inflammation of the oral mucosa. Determination of the underlying cause of an oral inflammatory condition relies on a thorough history, complete physical and oral examination, and incisional biopsy and histopathologic examination of lesions.

Article: http://www.vetsmall.theclinics.com/article/S0195-5616(13)00009-0/abstract

Pictures: http://www.sciencedirect.com/science/article/pii/S0195561613000090

Bullous pemphigoid and internal diseases – A case-control study.

Cristo Rey Intern — Sun, 26 May 2013 12:00:57 +0000

To study associations of bullous pemphigoid (BP) with internal diseases, we conducted a retrospective case control study assessing the frequency of selected diseases – diabetes mellitus, neurological diseases, malignant tumors, benign prostate hyperplasia, hypertension and ischemic heart disease in patients with BP. 89 patients with BP, whose data were retrieved from the register of the Centre of bullous diseases from the period of 1991-2006, were matched with 89 controls of the same age and gender, recruited from patients treated for other skin diseases. The frequency of internal diseases at the time of the onset of BP was evaluated by unconditional logistic regression adjusted for age and gender and maximum likelihood test for contingency tables. Neurological disease was found in 42.7% of the patients and in 19.1% of controls. This difference was statistically significant (p value = 0.001). Moreover, regression analysis has shown that patients with neurological disease in the age group >or= 80 years have significantly higher risk of pemphigoid than patients without neurological disease (odds ratio 10.55; 95% confidence interval 2.68 to 41.49). Most frequent were cerebral stroke in men and dementia in women. For other diseases and other age groups, no statistically significant influence was found.

European Journal of Dermatology.

“Coaches Corner” – New Coaches, New Perspectives

marc — Wed, 22 May 2013 16:08:58 +0000

Although everyday (whether I like it or not), I am reminded what it is like to live with Pemphigus and Pemphigoid, I am fortunate because I have the opportunity to share my story and build relationships.

Recently, the IPPF has welcomed two new Peer Health Coaches to our team, Mei Ling Moore (Los Angeles, CA) and Gloria Gutierrez (Orlando, FL). They both have been providing support for our community members for quite some time so it seemed only natural for them to volunteer as Peer Health Coaches. Both are compassionate listeners who actively participate on the IPPF website and Facebook page, communicate well with those that need support, provide relevant resources designed to improve patient/caregiver issues and make a difference in people’s lives by building long-lasting relationships.

I had the honor of seeing them in action recently at our annual Patient Conference in San Francisco and was amazed at how well they both provided confidence and hope to everyone they spoke with.

Please join me in welcoming Mei Ling and Gloria and feel free to reach out to them for peer advice.

Remember, you always have a “Coach” in your corner!

Targeted Delivery of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand To Keratinocytes with A Pemphigus Monoclonal Antibody

Cristo Rey Intern — Wed, 22 May 2013 12:00:17 +0000

We determined the feasibility of using an anti-desmoglein (Dsg) monoclonal antibody, Px44, to deliver a biologically active protein to keratinocytes. Recombinantly produced Px44-green fluorescent protein (GFP) injected into mice and skin organ culture delivered GFP to the cell surface of keratinocytes. We replaced GFP with tumor necrosis factor -related apoptosis-inducing ligand (TRAIL) to produce Px44TRAIL. We chose TRAIL as a biologic model because it inhibits activated lymphocytes and causes apoptosis of hyperproliferative keratinocytes, features of various skin diseases. Px44TRAIL formed a trimer, the biologically active form of TRAIL. Standard assays of TRAIL activity showed that Px44TRAIL caused apoptosis of Jurkat cells and inhibited interferon-γ production by activated CD4+ T cells. Enzyme-linked immunoassay with Px44TRAIL showed delivery of TRAIL to Dsg. Immunofluorescence with Px44TRAIL incubated on skin sections and cultured keratinocytes or injected into mouse skin, human organ culture or human xenografts detected TRAIL on keratinocytes. Px44TRAIL caused apoptosis of hyperproliferative, but not differentiating, cultured keratinocytes through binding to Dsg3. Foldon, a small trimerization domain, cloned into Px44TRAIL maintained its stability and biological activity at 37^o for at least 48 hr. These data suggest that such targeted therapy is feasible and may be useful for hyperproliferative and inflamed skin diseases.

Abbreviations:

Dsg, Desmoglein; GFP, Green fluorescent protein; TRAIL, tumor necrosis factor -related apoptosis-inducing ligand; HNSCC, head and neck squamous cell carcinoma; scFvs, single chain variable fragment antibodies; HA, hemaggultinin

Journal of Investigative Dermatology

The frequency of osteoporosis in patients with pemphigus vulgaris on treatment

Cristo Rey Intern — Tue, 14 May 2013 12:00:56 +0000

Background: Pemphigus vulgaris was almost fatal before the advent of glucocorticoids. Unfortunately, the high doses and prolonged administration of glucocorticoids, which often needed to control the disease, result in numerous adverse effects many of which are serious.

Aims: To evaluate the patients with pemphigus vulgaris on treatment in respect of osteoporosis and to compare the frequency of osteoporosis in these patients with the healthy ones.

Methods: The study consisted of 40 patients with pemphigus vulgaris and 34 healthy controls. Bone mineral density measurements were obtained by dual- energy X-ray absorptiometry. Blood serum, bone parameters, and biochemical hormonal measurements were examined in both groups.

Results: When the bone mineral density values of patients with pemphigus vulgaris were compared with those of the control group, there was no significant difference between hip bone mineral density values, while lumbar region T and Z scores were found significantly low in the patient group (p = 0.034 and p = 0.006, respectively). Osteoporosis, osteopenia, and normal dual-energy X-ray absorptiometry rates in the patient group were found to be 32.5%, 32.5%, and 35%, respectively. These rates were found to be 18%, 23%, and 59% in control group, respectively. There were more fractures in the patient group and the difference was statistically significant (p = 0.004).

Conclusion: An increase in osteoporosis frequency and secondary fracture to osteoporosis in the patients with pemphigus vulgaris was detected.

Full acticle can be viewed at: Indian Journal of Dermatology

Resistant oral mucosal lesions in pemphigus vulgaris responsive to double filtration plasmapheresis: First case report from Turkey.

Cristo Rey Intern — Fri, 10 May 2013 12:00:30 +0000

Background

Adjuvant therapeutic methods are employed when pemphigus vulgaris (PV) fails to be controlled by conventional corticosteroid treatment. Objective: The efficacy of double filtration plasmapheresis (DFPP) was investigated in a PV patient with severe, refractory mucosal disease.

Methods

A total of 3 DFPP cycles, each cycle consisting of 5 double filtration sessions conducted on alternate days was completed.

Results

DFPP provided immediate clinical relief of symptoms as well as a significant decrease in anti-desmoglein antibody levels and allowed for a much lower corticosteroid dose.

Conclusion

DFPP was an effective and safe adjuvant therapy in our patient with PV and it offers a valid treatment option in PV patients with recalcitrant disease.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

Prevalence and Clinical Significance of Anti-Laminin 332 Autoantibodies Detected by a Novel Enzyme-Linked Immunosorbent Assay in Mucous Membrane Pemphigoid

Cristo Rey Intern — Wed, 08 May 2013 12:55:23 +0000

IMPORTANCE A rare variant of mucous membrane pemphigoid (MMP) is characterized by circulating anti-laminin 332 (Lam332) autoantibodies and seems to be associated with concurrent malignant neoplasms.

OBJECTIVE To determine the prevalence and clinical significance of anti-Lam332 autoantibody detection from a large series of patients with MMP. DESIGN Multicenter retrospective study.

SETTING Four French national centers for autoimmune bullous diseases.

PARTICIPANTS One hundred fifty-four patients with MMP and 89 individuals serving as controls were included.

INTERVENTIONS Serum samples were analyzed by a new Lam332 enzyme-linked immunosorbent assay (ELISA); clinical and immunopathologic data were obtained from the patients’ medical records.

MAIN OUTCOME MEASURES The Lam332 ELISA scores were evaluated with respect to clinical characteristics, standard and salt-split indirect immunofluorescence, and bullous pemphigoid (BP) 230 and BP180-NC16A ELISAs.

RESULTS The Lam332 ELISA score was positive (≥9 U/mL) in 20.1% of serum samples from patients with MMP, 1 of 50 patients with bullous pemphigoid (BP), none of 7 with pemphigus, and 3 of 32 other controls. No relationship was evidenced between a positive ELISA Lam332 score and age; sex ratio; oral, ocular, genital, skin, or esophageal/laryngeal involvement; internal malignant neoplasm; or BP180 ELISA score. Salt-split skin indirect immunofluorescence and ELISA BP230 results were more frequently positive when Lam332 ELISA results were positive (P = .04 and .02, respectively). Patients with a positive Lam332 ELISA score frequently had more severe MMP (67.8% vs 47.2%; P = .04).

CONCLUSIONS AND RELEVANCE Results of this novel ELISA showed that serum anti-Lam332 autoantibodies are detected in 20.1% of patients with MMP. Anti-Lam332 autoantibodies are mainly detected in patients with severe MMP but not preferentially in those with a malignant neoplasm. The association between anti-Lam332 and anti-BP230 autoantibodies might arise from an epitope-spreading phenomenon.

JAMA dermatology (Chicago, Ill.)