6th July 2023

Other Blistering Disorders

Differential Diagnosis for a Blistering Rash

Vesicles and bullae are non-specific signs that arise from multiple causes, including physical, infectious, medication-related and immunobullous conditions.

Physical/chemical

• Friction blisters: commonly seen on palms, soles and heels
• Insect bites: may produce a localised blister
• Polymorphic light eruption: a common photosensitivity reaction that occurs hours to days following UV exposure. Presents on sun-exposed skin as itchy macules, papules, plaques and/or vesicles.
• Sunburn: presents with oedema, erythema and blistering in severe cases
• Burns: blistering seen in partial thickness burns

Infections

These conditions are explained in detail in the Infections section

• Bullous cellulitis/erysipelas: severe cases, associated with Group A beta-haemolytic streptococcus.
• Bullous impetigo: due to staphylococcal exfoliative toxins.
• Staphylococcal scalded skin syndrome (SSSS): an acute blistering rash caused by staphylococcal toxins. Primarily seen in children under 5 years old and noted in immunodeficient and renal failure patients.
• Herpes simplex virus (HSV) infection: a contagious vesicular condition affecting the skin and mucosal caused by HSV-1 and HSV-2.
• Eczema herpeticum: a dermatological emergency secondary to HSV infection presenting with widespread painful monomorphic blisters. Most frequently associated with atopic eczema.
• Herpes zoster infection: a self-limiting painful vesicular rash caused by the reactivation of the varicella zoster virus.

Drug eruptions

These conditions are explained in detail in the Allergy and sensitivity topic.

• Stevens-Johnson syndrome/Toxic Epidermal Necrolysis (SJS/TEN): an acute and life-threatening skin reaction that causes sheet-like skin and mucosal loss due to medications and infections. Culprit medications include allopurinol, anticonvulsants, antibiotics, allopurinol and NSAIDs.
• Fixed drug eruption: a cutaneous adverse drug reaction that recurs at the same site each time the individual is exposed to the drug. It is a delayed type IV hypersensitivity reaction and can present as a bullous, erythematous or pigmented rash. Culprit medications include antibiotics, analgesics, antihypertensives and anticonvulsants.

Immunobullous

• Pemphigus vulgaris: a potentially fatal autoimmune blistering disorder typically presenting <60 years. Intraepithelial blisters caused by IgG antibodies against desmoglein 3 and/or desmoglein 1.
• Pemphigus foliaceus: superficial, scaly and relatively benign form of pemphigus with no mucosal involvement.
• Drug-induced pemphigus: pemphigus precipitated by a medication. Causative agents include penicillamine, ACE inhibitors and piroxicam.
• Paraneoplastic pemphigus: pemphigus associated with underlying malignancy.
• Bullous pemphigoid: common autoimmune blistering typically present in the elderly. Subepidermal blistering caused by IgG antibodies against BP180 and/or BP230. Can be triggered by neurological disorders, medications and physical trauma (e.g. burns).
• Pemphigoid gestationis: Intensely itchy urticaria-like rash which develops into tense sub-epidermal blisters. Typically presents in the second and third trimester of pregnancy.
• Dermatitis herpetiformis: intensely itchy clusters of vesicles caused by gluten peptides triggering the production of IgA autoantibodies targeting the skin.

Other

• Eczema pompholyx: also called dyshidrotic eczema. This typically presents with clusters of vesicles on the palm and soles, palmoplantar hyperhidrosis and a history of atopic eczema.
• Porphyria cutanea tarda: the most common type of porphyria due to a defect in the liver enzyme, uroporphyrinogen decarboxylase. Excess porphyrin results in photosensitivity. This condition presents with painful blistering and crusting on sun-exposed skin, hyperpigmentation and red/tea-coloured urine.