International Pemphigus Pemphigoid Foundation

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.)

Desmosomal adhesion and pemphigus vulgaris: the first half of the story

Cristo Rey Intern — Wed, 08 May 2013 12:00:01 +0000

Pemphigus vulgaris (PV) is a paradigm of autoimmune disease affecting intercellular adhesion. The mechanisms that lead to cell–cell detachment (acantholysis) have crucial therapeutic implications and are currently undergoing major scrutiny. The first part of this review focuses on the classical view of the pathogenesis of PV, which is dominated by the cell adhesion molecules of the desmosome, namely desmogleins (Dsgs). Cloning of the DSG3 gene, generation DSG3 knock-out mice and isolation of monoclonal anti-Dsg3 IgG have aided to clarify the pathogenic mechanisms of PV, which are in part dependent on the fate of desmosomal molecules. These include perturbation of the desmosomal network at the transcriptional, translational, and interaction level, kinase activation, proteinase-mediated degradation, and hyper-adhesion. By the use of PV models, translational research has in turn helped shed light into the basic structure, function, and dynamics of assembly of desmosomal cadherins. The combined efforts of basic and applied research has resulted in tremendous advance into the understanding of epidermal adhesion and helped debunk old myths on the supposedly unique role of desmogleins in the mechanisms of cell–cell detachment in PV.

From: http://informahealthcare.com/doi/abs/10.3109/15419061.2013.763799

Oxidative stress and autoimmune skin disease.

Cristo Rey Intern — Sat, 04 May 2013 12:00:53 +0000

Antioxidants play the important role in our body of neutralizing free radicals and peroxides that are formed during normal physiologic events. While these reactive oxygen species are necessary for numerous biological processes, when created in excess they can have deleterious effects. The skin as an organ is constantly under attack by reactive oxygen species from both endogenous and exogenous sources. The pathophysiology of many autoimmune diseases is unknown and recently oxidative stress has come to light as a possible triggering mechanism. Recent investigations attempting to link autoimmune skin diseases and oxidative stress have had varying degrees of success. In this article, we review the current literature regarding antioxidants in alopecia areata, pemphigus vulgaris and other blistering diseases, vitiligo, and psoriasis, and suggest possible future studies and treatment options.

European journal of dermatology : EJD

Application for Tacrolimus Ointment in Treating Refractory Inflammatory Ocular Surface Diseases

Cristo Rey Intern — Fri, 26 Apr 2013 12:00:29 +0000

Purpose

To evaluate the therapeutic effects of topical tacrolimus ointment on refractory inflammatory ocular surface diseases.

Design

Retrospective interventional consecutive case series.

Methods

In Severance Hospital, Seoul, South Korea, 0.02% tacrolimus ointment was topically applied 1 to 3 times per day, depending on disease severity, for up to 31 months in eyes of 12 consecutive patients with refractory inflammatory ocular surface diseases who had previously been treated with steroid therapy. Seven patients had chronic cicatrizing conjunctivitis (6 cases caused by Stevens-Johnson syndrome and 1 attributable to ocular cicatricial pemphigoid); 4 had scleritis (3 necrotizing scleritis, 1 recurrent nodular scleritis); and 1 patient had Mooren ulcer with corneal perforation. The therapeutic outcomes after tacrolimus treatment were evaluated according to the following criteria: change in clinical findings (eg, decrease of hyperemia, ocular pain, epithelial defect, and pseudomembrane), intraocular pressure (IOP), and need for steroid therapy.

Results

In all 3 groups, tacrolimus showed an immunosuppressive effect, especially on scleritis and Mooren ulcer. These effects included suppression of corneoscleral melting and reduction of hyperemia. In chronic cicatrizing conjunctivitis, simultaneous topical tacrolimus while tapering steroid therapy suppressed inflammatory relapse. The elevated IOP in steroid responders recovered to normal range after successful tapering of steroid. No adverse side effects were noted after 1.5 to 31 months of continuous tacrolimus treatment.

Conclusion

The use of topical tacrolimus ointment is effective in controlling refractory inflammatory ocular surface disease, and can reduce the need for steroid use while reducing inflammation recurrence.

Full article available here: http://www.ajo.com/article/S0002-9394(12)00863-X/abstract

An attempt to develop mouse model for anti-laminin γ1 pemphigoid.

Cristo Rey Intern — Tue, 16 Apr 2013 12:00:07 +0000

BACKGROUND: We recently reported that the autoantibodies of anti-p200 pemphigoid sera react with laminin γ1 and renamed this entity as anti-laminin γ1 pemphigoid. However, it has not been clarified whether the anti-laminin γ1 autoantibodies, particularly those to the C-terminal integrin binding site, affect the dermoepidermal junction and cause subepidermal blisters.
OBJECTIVE: The aim of this study was to develop animal models for anti-laminin γ1 pemphigoid.
METHODS: We attempted to produce two mouse models for anti-laminin γ1 pemphigoid; (1) a passive transfer model: injection of rabbit IgG to shorter bacterial recombinant protein of the murine laminin γ1 C-terminal 107 amino acids, and (2) an active disease model: direct immunization to mice with this recombinant protein.
RESULTS: Immunoblotting revealed that 70% of patient sera reacted with the shorter recombinant protein of human laminin γ1 C-terminus. In the passive transfer model, rabbit IgG to the murine laminin γ1 C-terminus was deposited, without C3 deposition, at the epidermal basement membrane zone. In contrast, in the active disease model, direct immunofluorescence of mouse skin sections showed no deposition of either murine IgG or C3. Blister formation was not seen in either model both phenotypically and histopathologically.
CONCLUSION: In the two different mouse animal models for anti-laminin γ1 pemphigoid, although rabbit IgG to the recombinant laminin γ1 C-terminus bound to the epidermal basement membrane zone in passive transfer model, no obvious blister formation was seen. To reproduce skin lesions in mouse models for anti-laminin γ1 pemphigoid, further improvement should be needed.

http://www.jdsjournal.com/article/S0923-1811(13)00003-0/abstract

Carbon Dioxide Laser Treatment in Hailey-Hailey Disease: A Series of 8 患者.

Cristo Rey Intern — Fri, 12 Apr 2013 12:00:49 +0000

OBJECTIVES: Hailey-Hailey disease (HHD), or benign familial pemphigus, is a rare autosomal dominant genodermatosis characterized by the formation of blisters. Eruptions are usually located in large skin folds, and when blisters become infected the condition can be very painful and disabling. HHD is difficult to treat. Many topical and systemic treatments have been used to bring exacerbations under control, but none have achieved medium- to long-term remission.
PATIENTS AND METHODS: Retrospective study of 8 patients with HHD treated with carbon dioxide laser therapy in our hospital between 1999 and 2011. The patients’ mean age was 50.7 years. The 4 men and 4 women were followed for between 1 and 12 years.
RESULTS: Satisfactory outcomes were achieved for 6 of the patients. Clinical improvement was observed in more than 75% of the affected area in 4 patients and in 50% to 75% of the area in 2 patients. The effect of treatments was maintained over time. The poorest outcomes were observed in patients treated at lower potencies. When blistering recurred after treatment, a second laser session achieved a good response. We observed no adverse events other than slight changes in skin texture and pigmentation.
CONCLUSIONS: Carbon dioxide laser therapy was safe and effective in producing medium- to long-term improvement in HHD symptoms that were refractory to conventional treatments.

http://www.actasdermo.org/en/linkresolver/tratamiento-enfermedad-hailey-hailey-con-laser/S0001-7310(12)00538-8/

Lobar torsion after lung transplantation

Cristo Rey Intern — Wed, 10 Apr 2013 12:00:35 +0000

Lobar torsion is a rare complication after lung transplantation. Here we report a case of right middle lobe (RML) torsion after bilateral sequential lung transplantation (BLTx). This 30-year-old lady underwent BLTx for bronchiolitis obliterans due to paraneoplastic pemphigus. The right lower lobe of the donor lung was resected due to inflammatory change during procurement. The postoperative chest X-ray showed persisting RML infiltrates. Fever and leukocytosis were noted 1 week later. RML lobectomy was performed after the reconstructed chest computed tomography confirmed the diagnosis of RML torsion. Adult respiratory distress syndrome with unstable vital signs, refractory hypoxemia and respiratory acidosis occurred thereafter. After venoarterial extracorporeal membrane oxygenation support, the patient recovered slowly and was discharged 5 months after BLTx.

Full article can be purchased here: http://www.sciencedirect.com/science/article/pii/S0929664612005104

Drug-triggered pemphigus foliaceus

Cristo Rey Intern — Sat, 06 Apr 2013 12:00:45 +0000

Pemphigus foliaceus (PF) is the most common autoimmune skin disease of dogs and other animal species. Although PF can spontaneously affect dogs of any breed, it appears more prevalent in Akita Inus and chow chows in the United States. The primary lesions are large pustules which rupture easily and progress rapidly to erosions and crusts. Lesion distribution most often involves the face, nasal planum, and ears. One third of affected dogs have paw pad lesions. Skin lesions of PF can remain localized or involve the entire body. The diagnosis of PF in dogs is based on historical information, clinical signs, and the demonstration of acantholytic keratinocytes in vesicles or pustules. (Source: Advances in Small Animal Medicine and Surgery)

Article can be purchased from : http://www.advancesinsmallanimal.com/article/PIIS1041782612000230/abstract?rss=yes