What is the diagnosis and treatment for itchy red spots and blisters diffuse over the body?

Diagnosis and Management of Itchy Red Spots and Blisters Diffuse Over Body

Immediate Diagnostic Approach

The presence of diffuse itchy red spots and blisters requires urgent evaluation to distinguish between life-threatening conditions like Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and more benign causes like bullous pemphigoid or drug reactions. 1

Critical Initial Assessment

Perform a complete physical examination focusing on:

• Body surface area (BSA) involvement: Measure the percentage of skin with erythema and epidermal detachment separately using a Lund and Browder chart 1
• Mucous membrane involvement: Examine eyes, mouth, nose, genitalia, and perianal areas for erosions, blisters, or mucositis 1
• Lesion morphology: Distinguish between target lesions, purpuric macules, flat atypical targets, flaccid bullae, or areas of dusky erythema 1
• Nikolsky sign: Assess whether gentle lateral pressure causes skin sloughing 1
• Vital signs: Check for fever, tachycardia, or hypotension suggesting systemic involvement 1

Review of Systems to Identify Severity

Ask specifically about 1:

• Skin pain resembling sunburn
• Fever, malaise, myalgias
• Ocular discomfort or photophobia
• Oral, nasal, or genital sores
• Odynophagia or hoarseness
• Lymphadenopathy or facial/extremity swelling

Differential Diagnosis Based on Clinical Features

Life-Threatening: SJS/TEN (Requires Immediate Hospitalization)

If BSA involvement >10% with purpuric macules, flat atypical targets, or skin sloughing with mucous membrane involvement, admit immediately and discontinue all potential causative drugs. 1

Clinical features 1:

• Dusky erythema progressing to flaccid bullae and epidermal detachment
• Painful skin that feels like sunburn
• Hemorrhagic mucositis affecting multiple sites
• Lesions reaching maximum at 5-7 days after onset

Bullous Pemphigoid (Most Common Autoimmune Blistering Disease)

If patient is >70 years old with tense bullae on erythematous skin, symmetric distribution on flexural surfaces, minimal mucosal involvement, and no atrophic scarring, bullous pemphigoid is the most likely diagnosis. 1

Clinical features 1:

• Severely pruritic bullous dermatosis
• Tense blisters arising from inflamed skin
• Symmetric distribution (flexural limbs, inner thighs, abdomen)
• Rarely involves mucous membranes

Drug-Induced Bullous Reactions

Review all medications started within the past 1-6 months, particularly diuretics, psycholeptics, antibiotics, NSAIDs, and anticonvulsants. 1

Immune Checkpoint Inhibitor-Related (If Applicable)

Grade based on BSA involvement 1:

• Grade 1: <10% BSA, asymptomatic
• Grade 2: 10-30% BSA, symptomatic
• Grade 3: >30% BSA with pain limiting self-care
• Grade 4: >30% BSA with fluid/electrolyte abnormalities

Essential Laboratory Investigations

Immediate Workup

Order the following tests 1, 2, 3:

• Complete blood count with differential: Screen for eosinophilia, anemia, or hematologic malignancy
• Liver function tests: Evaluate hepatic causes
• Urea and electrolytes: Assess renal function
• C-reactive protein: Measure inflammatory response
• Glucose, magnesium, phosphate: Check metabolic status
• Coagulation studies: Assess bleeding risk

Infection Screening (If Febrile or Systemically Unwell)

• Blood cultures 1
• Mycoplasma and chlamydia serology 1
• Skin swabs for HSV and varicella zoster virus 1
• Chest X-ray if respiratory symptoms present 1

Definitive Diagnostic Tests

Obtain two skin biopsies: one from lesional skin (edge of fresh blister) for routine histopathology in formalin, and one from perilesional skin sent unfixed for direct immunofluorescence (DIF). 1

For bullous pemphigoid confirmation 1:

• DIF showing linear IgG and/or C3 deposits along dermoepidermal junction
• ELISA for anti-BP180 and anti-BP230 antibodies
• Indirect immunofluorescence on salt-split skin showing IgG binding to epidermal side

Treatment Algorithm

If SJS/TEN Suspected (BSA >10% with Mucosal Involvement)

Immediately discontinue all potential causative drugs, admit to intensive care or burns unit, and initiate IV methylprednisolone 1-2 mg/kg/day. 1

Additional management 1:

• Establish IV access through non-lesional skin
• Initiate fluid resuscitation if clinically indicated
• Insert nasogastric tube if unable to maintain oral intake
• Consult ophthalmology within 24 hours
• Consider calculating SCORTEN for prognosis

If Bullous Pemphigoid Suspected

For symptomatic bullae covering 10-30% BSA, initiate high-potency topical corticosteroid (clobetasol 0.05%) to affected areas and oral prednisone 0.5-1 mg/kg/day with taper over at least 4 weeks. 1

Local wound care 1:

• Apply plain petrolatum ointment to erosions
• Cover with non-adherent gauze and bandages
• Reassess every 3 days for progression

Steroid-sparing options 1:

• IVIG or rituximab for long-term management
• Consult dermatology for transition plan

If Immune Checkpoint Inhibitor-Related

Hold immunotherapy for Grade 2 or higher, initiate topical clobetasol, and have low threshold for systemic prednisone 0.5-1 mg/kg/day. 1

• Grade 1: Continue therapy with observation only
• Grade 2: Hold therapy, dermatology consultation
• Grade 3-4: Permanently discontinue, admit patient, IV methylprednisolone

If Mild Pruritic Rash Without Blisters

Begin with emollients, short course of non-sedating antihistamines (fexofenadine or loratadine), and topical hydrocortisone 1% applied 3-4 times daily. 2, 4

Common Pitfalls to Avoid

• Do not delay hospitalization if BSA involvement exceeds 10% with systemic symptoms—SJS/TEN mortality increases with delayed treatment 1
• Do not start systemic steroids empirically without confirming diagnosis, as this may worsen certain conditions like staphylococcal scalded skin syndrome 1
• Do not overlook medication review—drug-induced reactions are reversible if identified early 1, 3
• Do not perform only one biopsy—both histopathology and DIF are required for definitive diagnosis of autoimmune blistering diseases 1
• Do not use sedating antihistamines in elderly patients except in palliative care due to dementia risk 2, 3

When to Refer

Refer immediately to dermatology or admit to hospital if: 1, 3

• BSA involvement >10%
• Any mucous membrane involvement with blistering
• Systemic symptoms (fever, malaise, respiratory compromise)
• Diagnostic uncertainty between SJS/TEN and other blistering disorders
• Failure to respond to initial management within 3 days