|
BLISTERING DISEASES
1. INTRODUCTION
Blistering diseases are defined as skin disorders that primarily give rise to vesicles (i.e. 5 mm or less in diameter) or bullae (i.e. over 5 mm in diameter). Blisters are accumulation of fluid lying within or below the epidermis. Blistering diseases can be classified according to the site of cleavage (see table 1). Only the common conditions will be discussed below.
The diagnosis of blistering diseases can sometimes be aided by physical findings.
(i) Morphology of blister :
- Subepidermal blister occurs between the dermis and the epidermis. It contains thick wall and may contain blood.
- Intraepidermal or subcorneal blister usually has very thin roof. Intact blisters may not be easily detected but leaving erosions only.
Palm and sole blisters usually remain intact because of the thick stratum corneum.
- Grouped vesicles along a dermatome is characteristic of herpes infection.
(ii) Site of blister :
- Pompholyx occurs at palm and soles
- Blisters at sites of frequent trauma suggest of Epidermolysis Bullosa.
(iii) Mucosal membrane involvement is frequently found in pemphigus, erythema multiforme and fixed drug eruption.
Table 1 : Causes of Blistering Diseases
(A) Subcorneal Blisters :
1. Bullous Impetigo
2. Subcorneal Pustular dermatosis
3. Miliaria Crystallina
(B) Intra-epidermal Blisters
1. Acute Dermatitis e.g. eczema, contact dermatitis
2. Pompholyx
3. Herpes infections
4. Fixed Drug eruptions (epidermal type)
5. Friction Blisters
6. Erythema multiforme (epidermal type )
7. Pemphigus Vulgaris
(C) Subepidermal Blisters
1. Bullous Pemphigoid
2. Linear IgA Diseases
3. Dermatitis Herpetiformis
4. Erythema Multiforme (dermal type)
5. Fixed Drug Eruptions (dermal type)
6. Epidermolysis Bullosa
2. BULLOUS IMPETIGO
Usually caused by Staph. aureus and occasionally by Strep. pyogenes.
More common in children and mainly affects face and hands.
Bullae are flaccid and usually contain pus. When the pustules are ruptured, they give rise to golden crusts.
Diagnosis : Swab from pustules for culture
Treatment :
(i) Topical antibiotics (e.g. fusidic acid cream, chlortetracycline ointment) is good for localized infection.
(ii) Oral antibiotics (e.g. cloxacillin, erythromycin) for widespread lesions.
3. SUBCORNEAL PUSTULAR DERMATOSIS
A chronic, benign, relapsing, pustular eruption with unknown aetiology. Female is more commonly affected than male. The peak incidence occurring at the age of 40-50. The eruption occurs mainly in the groins, axillae, submammary areas and the flexor aspect of the limbs. The face is never affected, nor are the mucous membranes. Lesions usually start off as intact pustules which dry up within a few days, forming crusts or scales. Eruption tends to group together to form clusters with advancing edge.
Differential diagnosis : (i) Pustular psoriasis (ii) Impetigo
Diagnosis : Skin biopsy shows the presence of subcorneal pustules.
Treatment :
(i) Dapsone - Treatment of choice (50-100 mg/day)
(ii) Oral Steroid - less effective as compared with dapsone
4. MILIARIA CRYSTALLINA
This condition occurs in hot and humid climate when babies are wearing too many clothes. It leads to blockage of the sweat ducts. Clinically, numerous monomorphic clear vesicles without surrounding erythema are seen on the skin, usually the trunk. Typically the skin remains dry. The disease is self-limiting. Calamine lotion can be prescribed. Prevention is by avoiding prolonged hot, humid environment and overclothing.
5. ACUTE DERMATITIS (ACUTE ECZEMA)
Vesicles are common sign of acute dermatitis. They are usually associated with intense pruritus. Vesicles are easily ruptured because of self scratching and results in multiple excoriations.
Treatment : Refer to the Chapter 3
6. POMPHOLYX
A distinct pattern of acute dermatitis as characterized by acute onset of multiple itchy vesicles +/- bullae at palms and soles. Vesicles seldom rupture because of the thick stratum corneum. Usually, the cause is unknown but occasionally may be secondary to severe tinea infection or contact dermatitis occurring in other part of the body.
Treatment : Requires potent topical steroid (e.g. 0.025 % fluocinolone). Oral antibiotics (e.g. erythromycin) is indicated if there is evidence of secondary bacterial infection. In very severe case, a short course of oral steroid may be required.
7. HERPES INFECTIONS (HERPES SIMPLEX / HERPES ZOSTER)
Pain is the most useful symptom to differentiate blisters caused by herpes infections from other blistering disorders. Eczema or tinea infection give rise to itchy rather than painful vesicles.
In contrast to pemphigus or pemphigoid which may give rise to painful lesions, the vesicles of herpes infections are more localized.
8. FRICTION BLISTERS
It occurs at hands and feet. Diagnosis can be easily made from history e.g. wearing ill-fitting or new shoes.
9. FIXED DRUG ERUPTIONS
It is presented as well-circumscribed erythematous patches or bullae, frequently occurring at hands, penis and mouth. A characteristic feature is the recurrence of the same skin lesions at the same sites when patients are challenged by the same offending agents again. Lesions heal with circumscribed pigmentation.
Histologically, dermal or epidermal blisters can occur. Basal cell degeneration and pigmentary incontinence are often seen.
The common offending drugs include tetracycline, barbiturates, sulphonamides, phenolphthalein, salicylate and oxyphenbutazone.
The disease is self-limiting. Avoidance of offending drug is most important.
10. ERYTHEMA MULTIFORME
10.1 Aetiology and Pathogenesis
It is a hypersensitivity reaction to infections (e.g. herpes simplex, streptococcus, mycoplasma) or drug (e.g. penicillins, sulphonamides, barbiturates, piroxicam).
10.2 Clinical Features
Typically, discoid well-demarcated erythematous plaques with central blisters or central necrosis can be found at 4 limbs (i.e. target lesions). Occasionally, bullae with erythematous base can occur.
Stevens-Johnson syndrome is a severe form of erythema multiforme with mucosal involvement.
10.3 Diagnosis
The diagnosis can be confirmed by skin biopsy. The cause can sometimes be found by looking for primary site of infection (e.g. herpes) and by taking a detailed drug history.
10.4 Treatment
For mild cases, giving topical steroid may be all that is needed. For frequent recurrent attacks, one should look hard for the presence of herpes infection. Maintenance oral acyclovir treatment can be considered in the latter.
The beneficial effect of oral prednisolone in Stevens-Johnson syndrome is controversial.
11. PEMPHIGUS VULGARIS
11.1 Introduction : The disease occurs worldwide.
The incidence is 0.1-0.5/100,000
The peak incidence is between 4th-6th decade
11.2 Pathogenesis : Binding of autoantibody to antigen on the surface of keratinocytes which leads to inflammation and acantholysis.
11.3 C/F : It presents as blisters attacking the skin including mucosae (i.e. oral mucosa, conjunctiva). Intact blister is seldom seen because the roof of the blister is thin and is easily ruptured. Ruptured bullae lead to the formation of erosions. Nikolsky's sign (i.e. rubbing normal skin causes new lesion to form) is characteristic. Eruption tends to develop on the trunk and the face with sparing of the extremities (centripetal distribution). Involvement of the oral mucosa gives rise to painful ulcers.
11.4 Investigation :
(i) Skin biopsy for histology
This is done to confirm the diagnosis. In order to see the diagnostic features, new, rather than old lesion should be chosen for biopsy. Classically, one should find suprabasal blister with acantholysis in histology.
(ii) Skin biopsy for Direct Immunofluorescence (IMF)
Perilesional skin shows the presence of intercellular IgG deposition within the epidermis.
(iii) Indirect Immunofluorescence (Serology)
Serum from the patient allows the titre of the circulating anti-intercellular antibody to be measured. The titre correlates with the disease activity and is a good parameter for monitoring the disease progress. This test is not casually available. It can only be done in a few hospital-based centres with special arrangement.
(iv) Tzanck test
A cytology method revealing the characteristic acantholytic cells. It provides an instant diagnosis. However, it is seldom done since it requires expert cytologist and it also carries a significant false positive as well as false negative rates.
11.5 Management : Potentially lethal disease. Hospitalization is often required for close monitoring of disease progress. Hospitalization is particularly indicated if any one of the following conditions which signifies severe involvement occurs :
(i) Extensive cutaneous involvement
(ii) Systemic upset
(iii) Mucosal involvement other than oral cavity
(iv) High indirect immunofluorescence (IMF) titre
11.6 Topical Treatment
Potent topical steroids have to be used (e.g. clobetasol propionate). Usually given as an adjuvant therapy. Rarely, when skin lesions are very localized, then topical treatment can be given as a single therapy.
For oral lesions, one can try triamcinolone in orabase.
11.7 Systemic Treatment
(i) Oral Steroid
Prednisolone is the drug of choice. To control the acute attack, usually it requires a very high dose (i.e. > 60 mg daily) to start with. Occasionally, > 100 mg of prednisolone has to be prescribed. Steroid can be gradually tailed down to maintenance dose (i.e. 15-30 mg daily) once the disease is under controlled as indicated by no new eruption, low titre of anti-intercellular antibody. Watch out for complications especially silent infection.
(ii) Steroid-sparing Agents
Since a relatively high dose of prednisolone is usually required to control the disease, in order to prevent the long term side effects of oral steroid (e.g. opportunistic infections, osteoporosis), an immunosuppressant can be added for its steroid sparing effect. Commonly used immunosuppressants are :
(a) Azathioprine (2-3 mg/kg/day)
(b) Cyclophosphamide
(c) Methotrexate
The major side effects of azathioprine and methotrexate are marrow suppression and hepatotoxicity. Cyclophosphamide may give rise to haemorrhagic cystitis, infertility as well as marrow suppression.
Regular monitoring of CBP and LFT is needed when prescribing these steroid sparing agents.
11.8 Treatment of Recalcitrant Cases
(i) Plasmaphaeresis
This in-patient treatment is only available in major hospitals. The renal team in the hospital can be consulted for providing the treatment if it is indicated.
(ii) Pulse Methylprednisolone Therapy
(iii) Cyclosporin A
11.9 Indications of Treatment Response
(i) No new lesion develops
(ii) Healing of old lesions
(iii) Dropping circulating antibody titre (indirect IMF)
12. BULLOUS PEMPHIGOID
12.1 Introduction
It is about 2 times more common than pemphigus vulgaris.
Usually occurs in old age (i.e. >60).
It is present worldwide and affects male to female equally.
12.2 Pathogenesis
Production of autoantibody reacting with basement membrane zone which in turns leads to separation of epidermis from the dermis.
12.3 Clinical Features
Early lesions in form of urticarial plaques may precede bullae.
Presents as large intact blisters at lower abdomen, inner thighs, groin, axilla and flexures.
Mucosal lesions are less common and often less severe than Pemphigus Vulgaris.
12.4 Investigations
(i) Skin biopsy for histology
Fresh lesion often demonstrates subepidermal blisters with mixed dermal infiltrates, especially eosinophils.
(ii) Skin biopsy for Direct Immunofluorescence (IMF)
Direct IMF of perilesional skin shows linear deposition of IgG +/- C3 at dermal-epidermal junction (Basement membrane zone)
(iii) Indirect Immunofluorescence (Serology)
Circulating IgG or C3 to basement membrane zone can be detected in 75% of patients. The serology titre does NOT correlate with disease activity. Therefore, this test is seldom performed.
12.5 Management
Rough indication of severity
(i) Mild - < 20 lesions
(ii) Moderate - 20-40 lesions
(iii) Severe - > 40 lesions
If severe, patient needs hospitalization.
Drug Treatment :
(i) Localized and mild case - Potent topical steroid (e.g. Clobetasol propionate) alone may control the disease.
(ii) Generalized disease - Oral steroid
The dosage of prednisolone required for controlling the disease is usually less than that of pemphigus vulgaris.
One can start off with 40-60 mg prednisolone daily. When the disease is under control, gradually tails it down to maintenance dose.
Recalcitrant Cases :
(i) Adjuvant Immunosuppressant - e.g. azathioprine, cyclophosphamide, methotrexate. Bullous pemphigoid is more commonly found in old age. These patients are more prone to the side effects of these drugs. Regular monitoring of CBP and LFT are needed.
(ii) Pulse Methylprednisolone Therapy
(iii) Plasmaphaeresis
(iv) Cyclosporin A
(v) Dapsone
12.6 Prognosis
The disease is often self-limiting. Spontaneous remission occurs in 3-6 years time.
13. LINEAR IgA DISEASE
13.1 Introduction
A rare blistering disorder as characterized by linear IgA deposition in basement membrane zone.
13.2 Clinical Features
It has 2 subtypes
(i) Adult type (around 60)
(ii) Childhood type (average onset around age of 5)
Cutaneous Lesions
(i) Adult type : mainly affects trunk, face, perineum, hands and feet
(ii) Childhood type : perioral region and perineum are common sites
Blisters typically occur in clusters.
Mucosal Lesions
Besides cutaneous lesions, half of the patients have oral or even ocular involvement as well.
13.3 Investigations
(i) Skin biopsy for histology
In majority of the cases, the picture resembles Dermatitis Herpetiformis. Occasionally, some may simulate Bullous Pemphigoid histologically.
(ii) Direct Immunofluorescence (Direct IMF)
Characterized by linear IgA deposition in basement membrane zone (BMZ).
(iii) Indirect Immunofluorescence (Indirect IMF)
13.4 Treatment
(i) Dapsone - It is the drug of choice. Response usually occurs within 48 hours. One has to be careful of dose-dependent haemolytic anaemia. Before starting dapsone, check for G-6-P-D level.
(ii) Prednisolone - Used as an adjuvant therapy to dapsone or when the latter is contraindicated. Usual dosage is 5-30 mg per day.
(iii) Colchicine - Used in resistant cases.
(iv) Topical Treatment :
Potent topical steroid can be prescribed e.g. fluocinolone 0.025%
13.5 Prognosis
(i) Adult type - most patients remit within 2 years
(ii) Childhood type - 50% chance of remission within 3 years
14. DERMATITIS HERPETIFORMIS
14.1 Introduction
An uncommon skin condition with the peak incidence around 30-40 years of age. Male is more common than female.
14.2 Pathogenesis
In western countries, the disease usually associates with coeliac disease (Gluten enteropathy). In eastern countries, since coeliac disease is extremely rare, this association is not usually observed.
14.3 Clinical Features
Lesions are composed of excoriated and scabbed intensely itchy papules.
The sites of predilection are extensors of 4 limbs, buttocks and face.
Intact vesicles seldom seen since they are ruptured by self scratching. Lesions heal with no scarring.
14.4 Differential Diagnosis
(i) Scabies - Presence of burrows, other family members are affected and sparing of the face are features suggestive of scabies.
(ii) Acute eczema - Atopic eczema affects flexures more than extensors.
14.5 Investigations
(i) Skin biopsy for histology - Microabscess in dermal papillae is characteristic.
(ii) Direct Immunoflorescence - It shows granular IgA deposition in BMZ.
(iii) Screening for the presence of coeliac disease.
14.6 Treatment
(i) Dapsone - It is the drug of choice. After starting the treatment, symptoms should subside within 48 hours and rash should be cleared up within days. Side effects are haemolytic anaemia, methaemoglobulinaemia.
(ii) Sulphapyridine/sulphamethoxypyridazine
They are used when dapsone is contraindicated.
(iii) Gluten Free diet - It is useful only when the disease is associated with coeliac disease. Referring to dietitian if required. Dietary restriction is not easy to follow.
14.7 Prognosis
Spontaneous remission rate is low.
15. EPIDERMOLYSIS BULLOSA
15.1 Clinical Features
This is a extremely rare groups of hereditary blistering disorders which are characterized by blisters and erosions resulting from trivial trauma. Blisters occur soon after birth and mainly concentrate on bony prominence of 4 limbs.
An acquired form mimicking Bullous Pemphigoid known as epidermolysis bullosa acquisita (EBA) occurs in adults. Bullae tend to occur at sites of trauma. The IgG in these patients binds to the anchoring fibrils attached to the Lamina densa. EBA may be associated with underlying systemic diseases like SLE, inflammatory bowel disease, amyloidosis and internal malignancy.
15.2 Investigations
The diagnosis can be confirmed by skin biopsy for histopathology and electronmicroscopy. The latter is also useful in subtyping the disease.
EBA can be differentiated from bullous pemphigoid by the sodium chloride split skin test and immunofluorescence on the skin specimen. In EBA, the blister occurs below the split, whereas, the blister occurs on the roof of the split in bullous pemphigoid.
15.3 Treatment
For the hereditary EB, no effective treatment is available at present. Antenatal diagnosis and genetic counselling can be offered.
Systemic steroid can be useful in EBA.
|
