Several diseases may present with blisters or pustules.
There is no common condition that can be used as a “reference point” with which less usual lesions can be compared in the same way as rashes can be compared with psoriasis.
A different approach is needed for the assessment of blistering or pustular lesions, based on the history and appearance, and is summarised as the three Ds: development, duration, and distribution.
Development
Was there any preceding systemic illness as in chickenpox, hand, foot, and mouth disease, and other viral infections?
Was there a preceding area of erythema as in herpes simplex or pemphigoid? Is the appearance of the lesions associated with itching as in herpes simplex, dermatitis herpetiformis, and eczematous vesicles on the hands and feet?
Duration
Some acute blistering arises rapidly for example, in allergic reactions, impetigo, erythema multiforme, and pemphigus.
Other blisters have a more gradual onset and follow a chronic course as in dermatitis herpetiformis, pityriasis lichenoides, and the bullae of porphyria cutanea tarda.
The rare genetic disorder epidermolysis bullosa is present from, or soon after, birth.
Distribution
The distribution of blistering rashes helps considerably in making a clinical diagnosis.
The most common patterns of those that have a fairly constant distribution are shown.
Itching is a very useful symptom.
If all the accessible lesions are scratched and it is hard to find an intact blister it is probably an itching rash. Clinical features: widespread blisters
Chickenpox
Chickenpox is so well known in general practice that it is rarely seen in hospital clinics and is sometimes not recognised.
The prodromal illness lasts one to two days and is followed by erythematous lesions that rapidly develop vesicles, then pustules, followed by crusts in two to three days.
Crops of lesions develop at the same sites usually on the trunk, face, scalp, and limbs.
The oral mucosa may be affected.
The condition is usually benign.
Dermatitis herpetiformis
Dermatitis herpetiformis occurs in early and middle adult life and is characterised by symmetrical, intensely itching vesicles on the trunk and extensor surfaces.
The vesicles are superficial. The onset is gradual, but may occur rapidly.
The distribution is shown in the diagram. Variants of dermatitis herpetiformis are larger blisters forming bullae and erythematous papules and vesicles.
Associated conditions
Coeliac disease with villous atrophy and gluten intolerance may occur in association with dermatitis herpetiformis.
Linear IgA disease is a more severe, widespread disease, in which there are “linear” deposits of lgA along the basement membrane of the epidermis and not only at the tips of the papillae as in dermatitis herpetiformis.
Treatment is with dapsone or sulfapyridine together with a gluten free diet.
Erythema multiforme with blisters
Blisters can occur on the lesions of erythema multiforme to a variable degree; when severe, generalised, and affecting the mucous membranes it is known as Stevens–Johnson syndrome.
The typical erythematous maculopapular changes develop over one to two days with a large blister (bulla) developing in the centre of the target lesions.
In severe progressive cases there is extensive disease of the mouth, eyes, genitalia, and respiratory tract.
The blisters are subepidermal, although some basement membrane remains on the floor of the blister.
Pityriasis lichenoides varioliformis acuta
As the name implies lichenified papules are the main feature of pityriasis lichenoides varioliformis acuta (or Mucha–Habermann disease), but vesicles occur in the acute form.
Crops of pink papules develop centrally, with vesicles, necrosis, and scales resembling those of chickenpox hence the “varioliformis”.
There is considerable variation in the clinical picture, and a prodromal illness may occur.
The condition may last from six weeks to six months. No infective agent has been isolated.
The pathological changes parallel the clinical appearance with inflammation around the blood vessels and oedema within the dermis.
Pemphigoid
The bullous type of pemphigoid is a disease of the elderly in which tense bullae develop rapidly, often with a preceding erythematous rash, as well as on normal skin.
It is mainly seen in the elderly and is slightly more common in women.
The flexural aspects of the limbs and trunk and flexures are mainly affected. The bullae are subepidermal and persistent, with antibodies deposited at the dermo-epidermal junction.
Unlike pemphigus there is a tendency for the condition to remit after many months.
Another type of pemphigoid occurs in which there is scarring of the oral mucous membrane and the conjunctiva.
Occasionally localised lesions are seen on the legs with evidence of an immune reaction, but often the absence of circulating antibasement membrane antibodies.
This is a relatively benign condition and often responds to topical steroids.
Treatment is with corticosteroids by mouth, 40–60 mg daily in most patients, although higher doses are required by some.
Azathioprine aids remission, with reduced steroid requirements, but takes some weeks to produce an effect.
It is essential to check the serum thiopurine methyl transferase (TPMT) level before starting treatment.
Patients with low levels have impaired ability to metabolise azathioprine and are likely to suffer toxic effects.
Topical steroids can be used on developing lesions.
Chronic scarring pemphigoid affects the mucous membranes with small bullae that break down, leading to erosions and adhesions in the conjunctivae, mouth, pharynx, and genitalia.
There is also a localised type of pemphigoid occurring on the legs of elderly women that runs a benign self-limiting course.
Pemphigus
The most common form of pemphigus vulgaris is a chronic progressive condition with widespread superficial bullae arising in normal skin.
In about half of the cases this is preceded by blisters and erosions in the mouth.
The bullae are easily broken, and even rubbing apparently normal skin causes the superficial epidermis to slough off (Nikolsky sign).
These changes are associated with the deposition of immunoglobulin in the epidermal intercellular spaces.
It is a serious condition with high morbidity, despite treatment with steroids and azathioprine.
Pemphigus vegetans and pemphigus erythematosus are less common variants.
Clinical features: localised blisters
Pompholyx, which means “a bubble”, is characterised by persistent, itchy, clear blisters on the fingers, which may extend to the palms, with larger blisters.
The feet may be affected.
Secondary infection leads to turbid vesicle fluid.
Pompholyx may be associated with a number of conditions atopy, stress, fungal infection elsewhere, and allergic reactions.
It may occur as a result of ingesting nickel in nickel sensitive patients and a similar reaction has been reported to neomycin.
Pustular psoriasis is characterised by deep seated sterile blisters, often with no sign of psoriasis elsewhere hence the term palmopustular pustulosis.
Foci of sepsis have long been considered a causative factor and recent studies have shown a definite association with cigarette smoking.
The pattern of HLA antigens indicates that this may be a separate condition from psoriasis.
Bullous impetigo is seen in children and adults. Staphylococci are usually isolated from the blister fluid.
The blisters are commonly seen on the face and are more deeply situated than in the non-bullous variety.
Herpes simplex.
Primary infection with type 1 virus occurs on the face, lips, and buccal mucosa in children and young adults.
Type II viruses cause genital infection.
Itching may be severe.
Herpes zoster is due to varicella virus producing groups of vesicles in a dermatome distribution, usually thoracic, trigeminal, or lumbosacral.
It is more common after the fourth decade of life. Insect bite allergy.
Large blisters, which are usually not itching, can occur on the legs of susceptible individuals. Bullous drug eruptions.
Fixed drug eruptions can develop bullae, and some drugs can cause a generalised bullous eruption, particularly:
