Immunobullous disorders Flashcards
What age group of patients develop bullous pemphigoid?
Bullous pemphigoid often presents in people over 80 years of age, and mostly affects people over 50. It can occur in younger adults, but bullous pemphigoid in infants and children is rare.
The prevalence of bullous pemphigoid is greater in patients with which skin condition?
The risk of developing bullous pemphigoid is greater in people with psoriasis, and it can be precipitated by treatment of psoriasis with phototherapy.
Which two classes of drugs are associated with precipitating onset of bullous pemphigoid?
- The most common drugs associated with bullous pemphigoid are the PD1-inhibitor immunotherapies (such as pembrolizumab, nivolumab) used to treat metastatic melanoma and other cancers.
- Dipeptidyl peptidase four inhibitors (also called gliptins) used to treat diabetes (such as sitagliptin, saxagliptin, linagliptin and especially, vildagliptin) have also been reported to induce bullous pemphigoid. The median time to onset to bullous pemphigoid is 11 months after initiation of therapy.
What is the pathophysiology of bullous pemphigoid?
Bullous pemphigoid is the result of an attack on the basement membrane of the epidermis by IgG +/- IgE immunoglobulins (antibodies) and activated T lymphocytes (white blood cells). The target is the protein BP180 (also called Type XVII collagen), or less frequently BP230 (a plakin). These proteins are within the NC16A domain of collagen XVII. They are associated with the hemidesmosomes, structures that ensure the epidermal keratinocyte cells stick to the dermis to make a waterproof seal.
What are the features of bullous pemphigoid?
Bullous pemphigoid causes severe itch and (usually) large, tense bullae (fluid-filled blisters), which rupture forming crusted erosions.
Is bullous pemphigoid usually localised or widespread?
Bullous pemphigoid may be localised to one area, or widespread on the trunk and proximal limbs.
Name 4 potential complications of bullous pemphigoid.
- Bacterial staphylococcal and streptococcal skin infection and sepsis
- Viral infection with herpes simplex, varicella or herpes zoster
- Complications of treatment
- Underlying and associated diseases.
What investigation can be ordered to support a diagnosis of bullous pemphigoid? What will it show?
Pathological examination of bullous pemphigoid shows a split under the epidermis. A dermal neutrophilic infiltrate is usual but not always present. Eosinophils may be prominent.
Direct immunofluorescence staining of a skin biopsy taken adjacent to a blister highlights antibodies along the basement membrane that lies between the epidermis and dermis.
What is the treatment for bullous pemphigoid?
- Ultrapotent topical steroids to treat limited disease < 10% of body surface (eg, clobetasol propionate)
- Moderate potency topical steroids and emollients to relieve itch and dryness
- Systemic steroids
- Steroid-sparing medications on their own or in combination with steroids
- Antibiotics for secondary bacterial infection
- Pain relief
What is the definition of pemphigus vulgaris?
Pemphigus vulgaris is a rare autoimmune disease that is characterised by painful blisters and erosions on the skin and mucous membranes, most commonly inside the mouth
Who does pemphigus vulgaris mainly affect?
Pemphigus vulgaris affects people of all races, age, and sex. It most commonly appears between the ages of 30 and 60 years and is more common in Jews and Indians than in other races, presumably for genetic reasons.
What is the pathophysiology of pemphigus vulgaris?
The keratinocytes are cemented together at unique sticky spots called desmosomes. In pemphigus vulgaris, immunoglobulin type G (IgG) autoantibodies bind to a protein called desmoglein 3 (dsg3), which is found in desmosomes in the keratinocytes near the bottom of the epidermis. The result is the keratinocytes separate from each other, and are replaced by fluid (the blister). About 50% of patients with pemphigus vulgaris also have anti-dsg1 antibodies.
How does pemphigus vulgaris present?
Most patients with pemphigus vulgaris first present with lesions on the mucous membranes such as the mouth and genitals. Blisters usually develop on the skin after a few weeks or months, although in some cases, mucosal lesions may be the only manifestation of the disease.
Skin lesions appear as thin-walled flaccid blisters filled with clear fluid that easily rupture causing itchy and painful erosions. They most often arise on the upper chest, back, scalp, and face. Erosions in the skin folds may develop into vegetative lesions which are granular and crusted (pemphigus vegetans). The skin around the nails may be painful, red, and swollen.
How is a pemphigus vulgaris diagnosis confirmed?
Diagnosis of pemphigus vulgaris generally requires a biopsy from the skin adjacent to a lesion. Histology typically shows rounded-up and separated keratinocytes (acantholytic cells) just above the basal layer of the epidermis. Suprabasal clefting may be reported. See pathology of pemphigus vulgaris.
Pemphigus is confirmed by direct immunofluorescence staining of perilesional skin biopsy sections to reveal immunoglobulin (Ig)G antibodies or complement on the cell surfaces of keratinocytes.
What is the treatment for pemphigus vulgaris?
The primary aim of treatment of pemphigus vulgaris is to decrease blister formation, prevent infections and promote healing of blisters and erosions [4.5]. Systemic corticosteroids are the mainstay of medical treatment for controlling the disease, usually in the form of moderate to high doses of oral prednisone or prednisolone, or as pulsed intravenous methylprednisolone. Since their use, many deaths from pemphigus vulgaris have been prevented (the mortality rate dropped from 99% to 5–15%). Corticosteroids are not a cure for the disease but improve the patient’s quality of life by reducing disease activity. The doses of corticosteroids needed to control pemphigus vulgaris and the length of time on treatment may result in serious side effects and risks.
