Naveed Sami - Autoimmune Bullous Diseases: Approach and Management

Autoimmune Bullous Diseases: Approach and Management — read online for free the complete book (whole text) full work

Below is the text of the book, divided by pages. System saving the place of the last page read, allows you to conveniently read the book "Autoimmune Bullous Diseases: Approach and Management" online for free, without having to search again every time where you left off. Put a bookmark, and you can go to the page where you finished reading at any time.

Light

Font size:

↓

↑

Georgia Tahoma Arial Verdana

Reset

Interval:

↓

↑

Bookmark:

Make

1234567...73

Springer International Publishing Switzerland 2016

Naveed Sami (ed.) Autoimmune Bullous Diseases 10.1007/978-3-319-26728-9_1

1. Pemphigus Vulgaris

Ilya Shoimer 1, Russell X. Wong 1 and P. Rgine Mydlarski 2, 3

(1)

Division of Dermatology, University of Calgary, Calgary, AB, Canada

(2)

Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada

(3)

Richmond Road Diagnostic and Treatment Centres, 1820 Richmond Road SW, Calgary, AB, T2T 5C7, Canada

P. Rgine Mydlarski

Email:

Abstract

Pemphigus vulgaris (PV) is an autoimmune mucocutaneous blistering disorder for which early recognition and treatment are necessary to achieve a favourable prognosis. A multidisciplinary, patient-centred approach is required to optimize therapeutic outcomes. Systemic corticosteroids remain first-line treatment for PV patients, yet their optimal dosing regimen remains unknown. Further, various steroid-sparing adjuvants play an important role in the treatment of PV. As clinical trials in the field are limited by small sample sizes and a lack of standardized outcome measures, a therapeutic algorithm is presented to guide the management of PV patients.

Keywords

Pemphigus vulgaris Systemic steroids Dapsone Azathioprine Mycophenolate mofetil Cyclophosphamide Methotrexate Rituximab Tumor Necrosis Factor- Inhibitors Intravenous Immunoglobulin

Introduction

Pemphigus refers to a group of autoimmune bullous disorders that are characterized by blistering of the skin, mucous membranes or both. The two main types of pemphigus are pemphigus vulgaris (PV) and pemphigus foliaceus (PF), each with its own clinical subtypes. Less common variants include paraneoplastic autoimmune multiorgan syndrome (or paraneoplastic pemphigus), IgA pemphigus, and pemphigus herpetiformis. This chapter will focus on PV, a prototypical organ-specific autoimmune disorder.

The estimated incidence of PV is between one and five cases per million population per year [].

Mucosal disease precedes cutaneous involvement in the majority of cases. The oral mucosa is most frequently involved, with lesions affecting the hard and soft palate, tongue, floor of the mouth and labial mucosa. Occasionally, PV patients may present with a desquamative gingivitis. Conjunctival, nasal, pharyngeal, laryngeal, esophageal, genital and anal involvement are less common. Patients may complain of cutaneous (i.e., pain, pruritus), mucosal (i.e., dysphagia, dysuria, anogenital or ocular concerns) and/or systemic (i.e., weight loss) symptoms.

Skin disease is characterized by multiple, painful erosions, vesicles, or flaccid bullae (Fig. ). The Nikolsky sign may be elicited by applying a shearing force on intact skin and inducing blister formation. The Asboe-Hansen sign, also known as the Nikolsky II or indirect Nikolsky sign, is demonstrated by applying lateral pressure on the edge of a blister and extending the blister into clinically unaffected skin. The most commonly affected areas include the scalp, face, trunk and intertriginous regions. Rarely, nail involvement has been reported.

Fig. 1.1

Clinical features of pemphigus vulgaris. Flaccid blisters, erosions and crusting on the face ( a ) and back ( b ) of a 55-year-old man

Pemphigus vegetans, a rare subtype of PV, is typified by a localized vegetative or papillomatous response. There are two types of pemphigus vegetans: the Hallopeau type and the Neumann type []. In pemphigus vegetans of Hallopeau, pustular lesions predominantly involve the folds and heal into localized verrucous, hyperkeratotic plaques. Pemphigus vegetans of Neumann is more extensive, characterized by periorificial papillomas and results in the formation of excess granulation tissue.

In 1964, Beutner and Jordan demonstrated the presence of anti-epidermal antibodies in the serum of pemphigus patients []. The collective data support the pathogenicity of these antibodies in pemphigus patients.

PV is a complex polygenic disorder involving multiple genetic loci, many of which remain unknown. Association studies link HLA class II genes to PV, as over 95 % of patients carry either the DRB1*0402 or DQB1*0503 alleles [].

Up to 25 % of patients with pemphigus have another underlying immunologic disease []. These findings suggest that common genetic factors from clinically distinct disorders may underlie the susceptibility to autoimmune disease.

Genetic predisposition alone is not sufficient to cause the development of PV. Environmental factors seem to be required to initiate and perpetuate the disease process. However, an inducing agent cannot be identified in most patients. Occasionally, drugs, physical agents, contact allergens, viral infections, vaccinations, and diet have been implicated in the disease [].

If left untreated, PV has a mortality rate ranging from 60 to 90 % []. Overwhelming sepsis, fluid and electrolyte imbalances, impaired thermoregulation, as well as cardiac and renal failure are possible life-threatening complications of the disease. Systemic corticosteroids and adjuvant therapies have reduced the mortality rate of PV patients to approximately 10 %; yet, treatment-related complications are now the leading cause of morbidity and mortality. By understanding the molecular mechanisms that underlie pemphigus, researchers are developing novel targeted therapies for the management of PV.

Diagnosis

During the initial clinical encounter, the physician should look for signs and symptoms to support a diagnosis of pemphigus. A thorough evaluation for potential risk factors, triggers and comorbidities must be elicited. Validated scoring systems, such as the Autoimmune Bullous Skin Intensity and Severity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI), may be used to measure the extent and distribution of lesions.

To confirm the diagnosis of PV, biopsies must be performed for both routine pathology and direct immunofluorescence (DIF). A 4.0 mm punch excision from an early, small vesicle or the periphery of a larger blister should be obtained for histopathologic analysis. Routine histology reveals loss of cellular cohesion (acantholysis) in the suprabasilar layer of the epithelium (Fig. ). Enzyme-linked immunosorbent assays (ELISA) are a more sensitive method for measuring antibodies to desmoglein 1 and desmoglein 3. Lastly, immunoblot and immunoprecipitation may be used to identify specific autoantibody profiles.

Fig. 1.2

Immunohistology of pemphigus vulgaris. Suprabasilar clefting, blister formation ( a ) and acantholysis ( b ) in a tombstone pattern (H&E, 100 magnification). Circulating intercellular IgG autoantibodies revealing a chicken-wire, honey-comb, or fishnet pattern on indirect immunofluorescence ( c )

Management

A multidisciplinary approach is required to optimize patient care and outcomes. An experienced dermatologist must work closely with the patients general practitioner. Other specialists may play a supportive role for PV patients, including oral pathologists, otolaryngologists, ophthalmologists, gynecologists, urologists, internists and psychiatrists, among others [].

Allied health care professionals often work with patients to minimize their co-morbidities. Educated wound care specialists are particularly helpful in providing non-adhesive dressing recommendations. Proper dental care and good oral hygiene are required. A dietician may provide nutritional support for patients with severe oral disease and resultant malnutrition, as well as those with steroid-related complications (i.e., diabetes, hypertension, obesity). If needed, analgesics should be ordered to ensure adequate pain control. Infections should be promptly recognized and treated aggressively.

Next page

1234567...73

Light

Font size:

↓

↑

Georgia Tahoma Arial Verdana

Reset

Interval:

↓

↑

Bookmark:

Make

Similar books «Autoimmune Bullous Diseases: Approach and Management»

Look at similar books to Autoimmune Bullous Diseases: Approach and Management. We have selected literature similar in name and meaning in the hope of providing readers with more options to find new, interesting, not yet read works.

Elaine A. Moore

Autoimmune Diseases and Their Environmental Triggers

Zainab Jiyad

Handbook of Skin Disease Management

Anna Waśkiel-Burnat (editor)

Clinical Cases in Scalp Disorders (Clinical Cases in Dermatology)

Barbara Horváth (editor)

Autoimmune Bullous Diseases: Text and Review

Michael H. Crawford

Current Diagnosis & Treatment Cardiology

Tokarz

The Everything Guide to Lyme Disease

Joyce M.C. Teng

Therapy in Pediatric Dermatology: Management of Pediatric Skin Disease

Marcel F. Jonkman

Autoimmune Bullous Diseases: Text and Review

Dédée F. Murrell

Clinical Cases in Autoimmune Blistering Diseases

George Y. Wu (editor)

Atlas of Dermatological Manifestations of Gastrointestinal Disease

Oscar R. Colegio

Skin Diseases in the Immunosuppressed

Rafal Tokarz

The Everything Guide to Lyme Disease

Discussion, reviews of the book Autoimmune Bullous Diseases: Approach and Management and just readers' own opinions. Leave your comments, write what you think about the work, its meaning or the main characters. Specify what exactly you liked and what you didn't like, and why you think so.