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By Professor Paul Rutter, University of Portsmouth
Problem representation
Mr K has fluid-like blisters on both hands, which he says are painful and itchy. He has a history of dry, itchy skin and his GP has given him lots of creams to control this, but generally they haven’t helped too much. He cannot remember the names of the creams as his wife puts them on for him.
Your pharmacy delivers Mr K’s regular medicines to his house. You check his patient record and find that he has a long history of cardiovascular problems, age-related macular degeneration, and relatively recent diagnoses of vascular dementia (18 months) and heart failure (nine months).
It appears that his generalised itching had been treated as dermatitis, scabies and asteatotic eczema but with no resolution of symptoms. None of his regular medicines have changed over the last nine months.
His current list of medication is:
- Ramipril 10mg 1 od
- Nicorandil 20mg 1 bd
- Bisoprolol 5mg 1 od
- Furosemide 40mg 1 mane and 1 noon
- Isosorbide mononitrate 60mg MR 1 od
- Fexofenadine 120mg 1 od
- Paracetamol 500mg 1-2 qds prn
- Lucentis 0.5mg via intravitreal injection once a month given at eye clinic.
Hypothesis generation
A multitude of skin conditions can cause vesicles and blistering. It is therefore important to reduce
the number of conditions you need to consider.
In the case of Mr K, we know he is elderly and the rash is on his hands. This means that conditions associated with childhood (e.g. chickenpox), localised rashes not involving the hands (shingles – torso or face; chilblains – extremities such as toes and fingers; herpes simplex – mouth and genitalia); and generalised rashes (e.g. heat rash) can be discounted.
As the blistering on his hands is recent, skin conditions that have a chronic blistering history should initially be considered only as possibilities. The conditions you first need to consider are:
Likely diagnosis
- Bullous impetigo
- Contact dermatitis
- Dyshidrotic eczema
- Insect bites/stings
- Fixed drug eruption.
Possible diagnosis
- Bullous systemic lupus
- Dermatitis herpetiformis
- Diabetic bullae
- Polymorphic light eruption
- Transient acantholytic dermatosis (Grover disease).
Critical diagnosis
- Bullous pemphigoid
- Erythema multiforme.
Continued information gathering
We know that Mr K takes multiple medicines and that cutaneous drug reactions are common. These can manifest in a variety of morphological forms affecting all areas of the body. Typically, they occur shortly after taking the medicine but can occur days or weeks later or on re-exposure.
Studying the drug history of Mr K, it shows no recent new medicines or reintroduction of any previous medicine. On this basis, a medicine-related cause seems not to be the cause of his hand blistering.
Mr K describes his rash as itchy and painful, which suggests that bullous impetigo is not the cause as this causes only mild itching. To further rule this out, you could ask Mr K if he has any systemic symptoms, as these are usually present with bullous impetigo (and not with the other likely causes). Mr K says he feels okay in himself – no worse than normal. Bullous impetigo seems therefore not to be the cause.
Problem refinement
Dermatitis, dyshidrotic eczema and insect bites all cause moderate to severe itching and varying levels of pain. Insect bites tend to be clustered and localised. Inspection of Mr K’s hands will show the distribution of the blisters.
The blisters appear as relatively large fluid filled bullae, widely distributed on both palms and to a lesser extent on the insides of his fingers and wrist. No papules or pustules are observed and there is a lack of redness.
The fact that large bullae are present with a lack of other skin markers seems to rule out insect bites and also dermatitis.
At this point, dyshidrotic eczema seems to be most likely, especially as the blisters have recently appeared. However, dyshidrotic eczema blisters tend to be smaller than those seen in this case.
Key points: Bullous pemphigoid
- Rare autoimmune disease seen mainly in older people
- Skin biopsy of a blister would confirm a clinical diagnosis
- There is no cure; it may remit but can recur.
Resources
The International Pemphigus and Pemphigoid Foundation provides information and resources for healthcare professionals and patients: pemphigus.org
PEM Friends is a UK-based charity that supports pemphigus and pemphigoid patients and carers: pemfriends.org.uk.
Red flags
Looking at the list of possible diagnoses, all of which tend to be chronic, you know that Mr K does not have lupus or diabetes, so can rule out bullous systemic lupus erythematosus and diabetic bullae. Dermatitis herpetiformis and transient acantholytic dermatosis seem unlikely as there is no involvement of blisters elsewhere. Polymorphic light eruption is a possibility, but rash at other sun exposed sites would be expected.
Of the critical diagnoses, erythema multiforme seems very unlikely because of the nature of Mr K’s rash, and no involvement elsewhere. However, of some concern is the possibility that bullous pemphigoid could be implicated as Mr K reports a history of unresolved generalised itch that has been treated as various skin conditions.
He also has a history of dementia, both of which are associated with this rare skin condition.
Self-care options
Dyshidrotic eczema may respond to avoidance of aggravating factors but, in this case, none have been identified.
Management
Management of dyshidrotic eczema tends to be a combination of steroids and antihistamines. Mr K already takes fexofenadine, so introducing another antihistamine does not seem sensible.
Potent steroids can be tried, but as you cannot rule out bullous pemphigoid, Mr K should be referred urgently for further evaluation, even though treatment is similar to that for dyshidrotic eczema.
Safety netting
You tell Mr K that the blisters on his hands might be related to his generalised itching and that he needs to see his GP. As Mr K is 80 and infirm, you tell him that you can speak to the GP on his behalf to get an appointment. You talk to the GP and tell him that you are unsure of the diagnosis but cannot rule out bullous pemphigoid and are concerned for Mr K’s welfare. The GP agrees to see Mr K that day.
Causes: conditions to consider
Likely diagnoses
Contact dermatitis
Dermatitis causes redness, drying of the skin, irritation and pruritus to varying degrees, and might show papules and vesicles. Itching is a prominent feature and often causes the patient to scratch, which results in broken skin with subsequent weeping. The rash develops at
the site of exposure. If allergic in origin, there may be milder involvement away from the site of exposure.
Dyshidrotic eczema
This refers to the presence of abrupt onset crops of intensely itchy small vesicles or blisters on the palms of the hands and occasionally on the soles of the feet. Stress and heat are known to precipitate the condition.
Insect bites
Itching papules, which can be intense, are the hallmark symptom of insect bites. Papules can become firm and last for several days. Occasionally, they blister – normally as a result of scratching – and secondary bacterial infection can then occur. Bites often occur in groups, are asymmetrical and appear on exposed areas, such as the hands, ankles and face.
Bullous impetigo
Impetigo tends to start with a single red macule that develops into a pustule or vesicle, which then ruptures, releasing exudate that dries and crusts over into a characteristic honey colour. In the bullous form, bullae (1-2cm in diameter) are also present and are often more widespread. Systemic symptoms of malaise, fever and lymphadenopathy are often present.
Fixed drug eruption
A fixed drug eruption rash characteristically recurs at the same site on re-exposure to a medication. On the first occasion, the eruption may develop after weeks to years of regular ingestion of the drug, but subsequent episodes develop within minutes to hours of recommencing the implicated drug. Typically, the rash is a red patch that may blister. The hands are a common site, as are the feet and face.
Possible diagnoses
Bullous systemic lupus
A rare condition associated with systemic lupus erythematosus, this blistering rash affects exposed skin, so may be seen on the hands. Lesions appear quickly, vary in size and may exhibit mild itch.
Dermatitis herpetiformis
Dermatitis herpetiformis is a rare condition characterised by intensely itchy clusters of papules and vesicles. It is more often seen in middle-aged people, especially in men. It commonly involves the buttocks, elbows, knees and sacral region, with hand involvement being rare. The lesions usually exhibit a symmetrical distribution. On investigation, up to 90 per cent of patients are found to have a gluten enteropathy.
Diabetic bullae
Diabetic bullae, also known as bullosis diabeticorum, are blister-like lesions that occur spontaneously on the feet and hands of patients with diabetes. They are more common in men than women, and in patients with long-standing diabetes.
Polymorphic light eruption
Seen seasonally in the spring and summer, polymorphic light eruption can appear anything from several hours to one or two days after exposure to sunlight; it can take a few weeks to resolve. It affects body sites exposed to the sun and, as its name suggests, can take on a variety of forms, including a small, blistering rash. The presentation is always the same for each patient.
Transient acantholytic dermatosis (Grover disease)
Onset is sudden. The rash, which is itchy, exhibits small red papules and vesicles that typically affect the central back, mid chest and upper arms. Older males are most likely to be affected.
Critical diagnoses
Bullous pemphigoid
Pemphigoid is a rare, blistering autoimmune disorder that usually affects people over the age of 70 years who have neurological disease – particularly stroke, dementia and Parkinson’s disease. It causes severe itch and usually large bullae that rupture, forming crusted erosions. A dermatitis-like rash may be present for weeks before any blisters appear. Any part of the skin can be involved, but the most common sites are body folds, hands and feet. It is associated with high levels of morbidity and increased mortality.
Erythema multiforme
More common in young adults (aged 20-40 years), erythema multiforme is precipitated by previous infection or medication. Prodromal symptoms of fatigue, malaise and fever may be experienced. The rash starts peripherally before spreading centrally. It is symmetric and starts as papules before developing into target lesions (appearing as three concentric rings). It may affect the oral mucosal surfaces, where lesions develop as painful blisters. Serious visual complications such as keratitis and visual impairment can occur.
Now check your knowledge of blister-like rashes that present on the hands of elderly patients by answering the following multiple choice questions:
1. Which ONE of the following is a distinguishing feature of dyshidrotic eczema that affects the hands?
a. Hyperpigmented macules
b. Large, scaly plaques
c. Pustules
d. Raised, ring-like lesions
e. Vesicles on the palms and sides of the fingers
2. Which ONE of the following symptoms is often seen before the development of blisters in bullous pemphigoid?
a. Itching and redness
b. Hair loss
c. Joint pain
d. Fever
e. Nausea
3. Which ONE of the following is a common trigger for bullous pemphigoid?
a. Certain medications, such as diuretics and antibiotics
b. Cold weather
c. Excessive exercise
d. High fat diet
e. High salt intake
4. Which ONE of these blistering skin conditions is often seen in patients with coeliac disease and involves itchy blisters on the elbows, knees and buttocks but can also affect the hands?
a. Bullous impetigo
b. Dermatitis herpetiformis
c. Erythema multiforme
d. Polymorphic light eruption
e. Transient acantholytic dermatosis
5. Which ONE of the following conditions, often involving the hands, may be precipitated by medication?
a. Benign familial pemphigus
b. Bullous systemic lupus
c. Contact dermatitis
d. Epidermolysis bullosa
e. Erythema multiforme
Answers
- e, 2. a, 3. a, 4. b, 5. e.
Learning
In Learning
This is your ultimate guide to pharmacy learning. Here you can find modules, articles, scenarios and more to improve your knowledge and support your learning in the pharmacy.