LAUSR

Autoimmune blistering dermatosis (AIBD) are potentially lethal, chronic relapsing disorders affecting the skin and mucous membranes which are mainly associated with IgG autoantibodies against distinct adhesion proteins of the epidermis or basement membrane zone (BMZ). Pemphigus is characterized by mucocutaneous blistering caused by IgG autoantibodies against desmogleins 3 and 1, which induce loss of cohesion between epidermal keratinocytes. In bullous pemphigoid, extensive pruritus and formation of tense blisters are driven by IgG autoantibodies against hemidesmosomal proteins, i.e. bullous pemphigoid (BP) 180 and BP230. Since the advent of systemic immunosuppressants, the overall mortality of AIBD has substantially decreased over the recent years although iatrogenic comorbidities have significantly increased. Treatment of AIBD largely depends on glucocorticoids which are often accompanied by adjuvant steroid-sparing immunosuppressants. In the majority of patients, systemic glucocorticoids are the first-line treatment to achieve disease control but their side-effects are significant and potentially life-threatening. Recent evidence suggests that the use of rituximab as a first-line therapy in pemphigus is associated with higher remission rates and reduced cumulative steroid doses compared to standard immunosuppressive therapy. Likewise, topical steroids and, presumably, doxycycline are suitable first-line options for BP, with a favourable safety profile compared to systemic glucocorticoids. Still, pemphigus and BP are associated with an increased risk of death. Infections are among the leading cause of death in these patients. In this issue of the Journal, Ren Z. and colleagues investigated the occurrence of serious infections in pemphigus and pemphigoid patients, based on a 10-year analysis of the Nationwide Inpatient Sample, a US database including a 20% representative sample of all US hospital inpatient admissions occurring each year. Compared with a control group, consisting of all hospitalized patients with unrelated diagnoses, patients with pemphigus or pemphigoid showed a higher incidence of infectious comorbidities including cutaneous and systemic fungal infection, viral infections, in particular herpes simplex and herpes virus, and bacterial infections of skin, bones, respiratory, gastrointestinal, genitourinary tract and central nervous system, septicaemia and antibiotic-resistant infections. As expected, the co-existence of comorbidities, such as diabetes and malignancies, as well as of other autoimmune diseases, significantly increased that risk. The authors point out that their findings may be biased as the here documented inpatients with pemphigus and pemphigoid may have a more severe disease course than patients with AIBD seen as outpatients. Of note, patients with pemphigus, but not pemphigoid, were found at higher risk of opportunistic infections, including aspergillosis and Pneumocystis carinii pneumonia. This may be related to the more profound immune suppression needed for initial clinical disease control of pemphigus compared with pemphigoid. A large retrospective study by Amber et al. found that the risk of Pneumocystis pneumonia was lower among AIBD patients compared to those with other dermatologic diseases requiring long-term immunosuppression. On the other hand, there are documented cases of Pneumocystis pneumonia in pemphigus patients treated with the anti-B-cell monoclonal antibody, rituximab. Given the expanding use of rituximab both in na€ıve pemphigus patients and in the maintenance phase, the effective need of antibiotic prophylaxis against this pathogen is a critical issue worth being further investigated in the setting of prospective studies or systematic reviews and meta-analyses. In spite of a slightly different profile of associated infections, Clostridium difficile enterocolitis, endocarditis and septicaemia were common causes of infection-related deaths in both groups. Based on these findings, which strategies should dermatologists adopt to reduce the incidence of infections, and the resulting mortality, in these patients? It should be noted that some of the infections reportedly increased in this study, such as pneumonia or herpes zoster, are vaccine-preventable infectious diseases. Validated recommendations for vaccinations do already exist for immunosuppressed patients with rheumatic diseases and psoriasis, respectively, and have been recently proposed for pemphigus as well. Apart from live vaccines, inactivated vaccines, such as those against pneumococcal infection and influenza, or the recently developed herpes zoster recombinant subunit vaccine, were shown to be safe and effective in immunosuppressed patients. Even though the vaccination-induced immune response may be weaker compared to immune-competent individuals, partial protection may be still preferred over no protection. Likewise, the use of probiotics may be considered in hospitalized AIBD patients or those requiring prolonged use of antibiotics to reduce the incidence of Clostridium difficile enterocolitis. Conversely, other infections, such as endocarditis or bone infections, are often challenging to diagnose due to their nonspecific symptoms and the delay in making the proper diagnosis