Skin peeling and erythroderma

Skin peeling is shedding of the stratum corneum or of the entire epidermis. Erythroderma is erythema with scaling over more than 90% of the body surface and is a dermatological emergency because of failure of skin barrier and thermoregulatory function.

Classification by pattern. Generalised erythema with scale (erythroderma). Generalised desquamation without erythema, usually after febrile illness (scarlet fever, toxic shock syndrome, Kawasaki disease, drug fever). Sheet like detachment of the epidermis with blistering (staphylococcal scalded skin syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis). Localised peeling of hands and feet (tinea, dyshidrotic eczema, keratolysis exfoliativa, contact dermatitis, hand foot and mouth disease).

Causes of erythroderma. A pre-existing dermatosis (psoriasis, atopic dermatitis, seborrhoeic dermatitis, pityriasis rubra pilaris) is the commonest cause. Drug reaction follows, then lymphoma (Sezary syndrome and mycosis fungoides), and a group that remains idiopathic. Proportions vary by region and age.

Mechanisms. Dermal vasodilation raises skin blood flow and heat loss. Epidermal turnover rises and scale carries protein, iron and folate loss. Cytokine release drives systemic inflammation.

Complications. Hypothermia or fever, fluid and electrolyte loss, hypoalbuminaemia, high output cardiac failure, secondary infection and sepsis, venous thromboembolism, and nutritional loss.

Key distinction. Acute onset over days suggests a drug or withdrawal of therapy. Gradual evolution over months suggests a pre-existing dermatosis, lymphoma or idiopathic erythroderma.

History

• Tempo of onset, pre-existing skin disease, recent withdrawal of oral corticosteroids, methotrexate or ciclosporin, or potent topical corticosteroids (precipitates psoriatic erythroderma).
• Drugs in the preceding 2 to 8 weeks: allopurinol, carbamazepine, phenytoin, lamotrigine, phenobarbital, sulphonamides, beta lactams, vancomycin, NSAIDs, lithium, isoniazid, captopril, terbinafine, cimetidine, gold.
• Fever, rigors, itch, thirst, weight loss, night sweats, fatigue.
• HIV risk, atopy, malignancy, recent infection, sun exposure, topical agents including herbal and traditional preparations.
• Sleep and itch burden.

Examination

• Temperature (can be low or high), pulse, blood pressure, respiratory rate, oedema, urine output.
• Percentage of body surface involved, colour, scale (fine, large, thick), fissures, lichenification, pustules, bullae, erosions, mucosal involvement.
• Clues to cause: nail pitting and onycholysis (psoriasis), palmoplantar keratoderma and islands of spared skin (pityriasis rubra pilaris), ectropion, hair loss, leonine facies (Sezary), lymphadenopathy, hepatosplenomegaly, atopic stigmata.
• Features of sepsis, dehydration and cardiac failure.
• Scabies burrows or crusting in immunocompromised patients.

Red flags

• Hypotension, tachycardia over 120, confusion, oliguria, temperature under 36 C or over 38.5 C.
• Pustules, skin pain, mucosal erosions or detachment.
• Facial oedema, eosinophilia, organ involvement (DRESS).
• Lymphadenopathy over 1.5 cm or hepatosplenomegaly.
• Erythroderma in a neonate or infant.
• Heart failure signs, pulmonary oedema.
• New erythroderma in an HIV positive or immunosuppressed patient.

Special groups

• Neonates and infants: ichthyoses, Netherton syndrome, staphylococcal scalded skin syndrome, immunodeficiency and metabolic disease.
• Older adults: drug reactions and lymphoma are more frequent, and cardiac failure is a greater risk.
• Pregnancy: generalised pustular psoriasis of pregnancy and drug reactions.
• Region specific: crusted scabies, HIV associated disease and traditional remedy reactions.

Pre-existing dermatosis

• Psoriasis, including after corticosteroid withdrawal.
• Atopic dermatitis.
• Seborrhoeic dermatitis.
• Allergic contact dermatitis.
• Pityriasis rubra pilaris.
• Lichen planus.
• Pemphigus foliaceus.
• Chronic actinic dermatitis.
• Ichthyoses and Netherton syndrome.

Drug related

• Morbilliform drug eruption evolving to erythroderma.
• DRESS.
• Acute generalised exanthematous pustulosis.
• Early Stevens-Johnson syndrome and toxic epidermal necrolysis.

Malignant and lymphoproliferative

• Sezary syndrome.
• Mycosis fungoides, erythrodermic.
• Leukaemia cutis.
• Paraneoplastic erythroderma from solid tumours.
• Adult T cell leukaemia lymphoma.

Infective

• Staphylococcal scalded skin syndrome.
• Toxic shock syndrome.
• Scarlet fever.
• Crusted scabies.
• Extensive dermatophytosis.
• HIV associated erythroderma.
• Kawasaki disease (peeling phase).

Other

• Acute graft versus host disease.
• Dermatomyositis.
• Sarcoidosis.
• Idiopathic erythroderma.

Step 1. Resuscitate and assess for complications. Obtain vital signs, fluid status, glucose and lactate.

Step 2. First line tests

• Full blood count with differential: eosinophilia in atopic disease, drug reaction or lymphoma; leucocytosis; lymphocytosis; atypical or Sezary cells.
• Urea, creatinine, electrolytes (hypernatraemia, hypokalaemia, hypocalcaemia), albumin, liver tests, calcium, magnesium, phosphate, glucose, CRP, LDH (raised in lymphoma), creatine kinase.
• Blood and skin cultures when febrile, with skin swab for Staphylococcus aureus.
• HIV test, hepatitis B and C serology, and an interferon gamma release assay or tuberculin test before ciclosporin, methotrexate or biologic therapy.
• Total IgE (atopic disease), pregnancy test.
• Skin scrapings for mites and fungal microscopy.
• ECG, and troponin when DRESS is suspected.
• Urinalysis.

Step 3. Skin biopsy. Obtain 2 to 3 punch biopsies (4 mm) from different sites, including an untreated area. Histology is nonspecific in about half of cases and should be repeated if the diagnosis stays unclear. Direct immunofluorescence for blistering or foliaceus features.

Step 4. Targeted tests

• Sezary syndrome: peripheral blood flow cytometry (CD4 to CD8 ratio of 10 or more, CD4 positive CD26 negative cells 30% or more, or CD4 positive CD7 negative cells 40% or more), T cell receptor clonality in blood and skin, and absolute Sezary cell count of 1000 cells/microlitre or more.
• Excisional lymph node biopsy for nodes over 1.5 cm or firm.
• CT of chest, abdomen and pelvis when lymphoma is suspected.
• Patch testing in contact dermatitis once the skin is stable.
• IL36RN gene testing in pustular psoriasis in selected cases.

Limits. The cause remains unidentified in a proportion despite complete evaluation. Drug rechallenge is not advised.

Immediate. Admit every patient with generalised erythroderma. Provide intravenous fluids when dehydrated or hypotensive (isotonic crystalloid 500 mL boluses, directed by blood pressure and urine output, with caution in cardiac failure). Keep the ward at 28 to 30 C and monitor core temperature. Provide analgesia, a high protein diet (about 1.5 g/kg daily) and electrolyte replacement. Stop all nonessential drugs, especially those started in the previous 8 weeks.

Skin care. Apply emulsifying ointment or 50% white soft paraffin with 50% liquid paraffin liberally every 2 to 4 hours, with wet wraps for severe disease. Avoid tar, dithranol, salicylates, other irritants and sensitisers. Use mild or moderate potency topical corticosteroids (hydrocortisone 1% or mometasone furoate 0.1% once daily) cautiously, mainly in eczema, drug reactions and idiopathic disease. Avoid strong topical agents in psoriasis because of systemic absorption and relapse.

Prevention of complications

• Enoxaparin 40 mg subcutaneously once daily until mobile (20 mg daily when creatinine clearance is under 30 mL/min). Monitor platelets and renal function.
• Treat infection: flucloxacillin 1 to 2 g intravenously every 6 hours (clarithromycin 500 mg intravenously or orally twice daily if penicillin allergic). Add vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours with level monitoring if MRSA is possible.
• Monitor for cardiac failure and protein loss.
• Chlorphenamine 4 mg orally at night for itch (avoid in glaucoma and urinary retention).

Cause directed

• Drug eruption: stop the culprit. For DRESS give prednisolone 0.5 to 1 mg/kg orally daily (maximum 80 mg daily), tapered over 6 to 12 weeks. Monitor eosinophils, liver tests, creatinine, troponin and creatine kinase twice weekly at first.
• Erythrodermic psoriasis:
• Ciclosporin 2.5 to 5 mg/kg orally daily in 2 doses for rapid control (monitor blood pressure and creatinine; avoid in uncontrolled hypertension and renal impairment).
• Infliximab 5 mg/kg intravenously at weeks 0, 2 and 6 (screen for tuberculosis and hepatitis B; avoid in heart failure of NYHA class 3 or 4).
• Methotrexate 7.5 to 25 mg orally weekly with folic acid 5 mg weekly on a different day (reduce when eGFR is under 60 mL/min; avoid when under 30 mL/min; monitor blood count and liver tests).
• Acitretin 10 to 25 mg orally daily, increased to 25 to 50 mg daily (maximum 50 mg daily); avoid in women of reproductive age unless reliable contraception is used and for 3 years after stopping; monitor liver tests and lipids.
• Interleukin 17 and interleukin 23 inhibitors are used by specialists.
• Atopic dermatitis: ciclosporin 3 to 5 mg/kg orally daily in 2 doses, dupilumab 600 mg subcutaneously then 300 mg every 2 weeks, or azathioprine 1 to 3 mg/kg orally daily after TPMT or NUDT15 testing (monitor blood count and liver tests). Short prednisolone courses help temporarily but risk rebound.
• Pityriasis rubra pilaris: acitretin 0.5 to 1 mg/kg orally daily, methotrexate or a biologic, under specialist care.
• Sezary syndrome and mycosis fungoides: specialist treatment (extracorporeal photopheresis, low dose methotrexate, bexarotene, mogamulizumab 1 mg/kg intravenously weekly for 4 weeks then every 2 weeks).
• Crusted scabies: ivermectin 200 micrograms/kg orally with food on days 1, 2 and 8 (add days 9, 15, 22 and 29 for severe disease) with permethrin 5% cream daily for 7 days then twice weekly until cure, and a keratolytic emollient. Not for children under 15 kg or in pregnancy. Treat contacts and isolate.
• Staphylococcal scalded skin syndrome and toxic shock syndrome: urgent antibiotics (flucloxacillin plus clindamycin 600 to 900 mg intravenously every 8 hours), source control and supportive care. Intravenous immunoglobulin 1 g/kg on day 1 then 0.5 g/kg on days 2 and 3 for severe streptococcal toxic shock.
• Postinfectious or drug fever desquamation: reassurance and emollients.

Monitoring. Temperature at least 4 times daily, daily weight, fluid balance, daily electrolytes, creatinine, albumin and glucose, and blood count twice weekly. Review for infection each day.

Referral and escalation. Same day dermatology for all erythroderma. Haematology and oncology for suspected lymphoma. Intensive care for sepsis, shock, respiratory compromise or heart failure. Infectious diseases for immunosuppressed patients. Ophthalmology for ectropion or conjunctival disease.

Admission and discharge. Admit all patients with erythroderma. Discharge when haemodynamically stable, temperature controlled, skin improving and a maintenance plan is in place, with review in 1 to 2 weeks. Safety net advice: return for fever, spreading redness, pus, breathlessness, ankle swelling, new blistering or inability to care for the skin.