A case of exfoliative dermatitis: initial work up and treatment

 A case of exfoliative dermatitis: initial work up and treatment

Assessment Summary

35-year-old man with acute generalized exfoliative dermatitis (erythroderma) involving most of the body surface area, etiology initially unknown. This is a dermatologic emergency due to risks of:

• Fluid/electrolyte and protein loss → dehydration, AKI, edema
• Thermoregulatory failure → hypothermia/hyperthermia
• High-output cardiac strain
• Malnutrition and catabolism
• Secondary bacterial infection and sepsis

Immediate priorities: stabilize (vitals, fluids, temperature, barrier), stop possible culprit drugs, and launch focused diagnostic workup while starting safe empiric anti‑inflammatory therapy.

Assume hospital admission to a monitored bed (or ICU/burn unit if unstable).

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Differential Diagnosis / Working Diagnosis

Working diagnosis: Acute erythroderma / exfoliative dermatitis, etiology undifferentiated.

Initial differential (prioritized for a 35‑year‑old male):

1. Drug-induced erythroderma / DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)
   – Recent new meds (2–8 weeks) such as antibiotics, antiepileptics, allopurinol, sulfonamides, etc.
   – Fever, facial edema, lymphadenopathy, eosinophilia, LFT elevation.

2. Psoriatic erythroderma
   – History of psoriasis, nail pitting/onycholysis, scalp plaques, islands of sparing; possible recent systemic steroid withdrawal.

3. Eczematous / atopic erythroderma
   – Personal/family atopy, severe pruritus, lichenification, flexural predominance, history of chronic eczema/contact dermatitis.

4. Cutaneous T‑cell lymphoma (CTCL), including Sézary syndrome
   – Persistent erythroderma, intractable pruritus, lymphadenopathy, palmar/plantar keratoderma, alopecia, B symptoms, abnormal lymphocytes.

5. Other dermatoses
   – Pityriasis rubra pilaris (PRP) (orange hue, follicular keratosis, islands of sparing)
   – Crusted scabies (hyperkeratotic plaques, nail involvement, institutional contact)
   – Less likely: connective tissue disease, paraneoplastic erythema, extensive dermatophytosis incognito, contact dermatitis.

SJS/TEN should be rapidly excluded (dominant pain > itch, dusky/targetoid lesions, mucosal erosions, positive Nikolsky, epidermal detachment).

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Workup Plan

1. Immediate triage & monitoring (first 0–2 hours)

• Level of care

  • Admit to monitored unit. Escalate to ICU/burn unit if: hemodynamic instability, rapid progression, extensive erosions/denudation, significant mucosal involvement, or concern for SJS/TEN/sepsis.

• Monitoring

  • Vitals q2–4h (continuous if unstable), pulse oximetry.
  • Strict input/output; consider Foley catheter if unable to monitor urine accurately (goal ≥0.5 mL/kg/hr).
  • Baseline weight; daily weights.
  • Cardiac monitoring if tachycardic or significant comorbidities.

2. History (obtained as soon as feasible)

Key elements:

• Onset and progression: days vs weeks; prior localized rash that generalized vs de novo.
• Medications in last 2–3 months: prescription, OTC, supplements, herbals; exact start/stop dates. Highlight:
  • Antibiotics (especially sulfonamides, penicillins, cephalosporins, minocycline)
  • Allopurinol, antiepileptics (phenytoin, carbamazepine, lamotrigine, phenobarbital), dapsone, antiretrovirals, immune checkpoint inhibitors, NSAIDs.
• Past dermatologic history: psoriasis, eczema, atopic dermatitis, contact dermatitis, prior erythroderma or phototherapy.
• Systemic symptoms: fever, chills, malaise, facial swelling, dyspnea, cough, GI symptoms, jaundice, weight loss, night sweats.
• Mucosal symptoms: oral, ocular, genital erosions or pain.
• Pruritus vs pain predominance.
• Lymphadenopathy, arthralgias, muscle weakness.
• Sexual history, HIV risk factors, TB exposures, travel, new contacts or institutional exposure (scabies).
• Personal/family history of atopy, psoriasis, autoimmune disease, lymphoma or other malignancy.
• Alcohol and substance use (important for liver function, methotrexate suitability).

3. Physical Examination

• Skin
  • Estimate BSA involvement; describe erythema and scale (fine vs thick/micaceous; orange hue; islands of sparing; follicular keratotic papules).
  • Look for targetoid lesions, dusky skin, bullae, erosions, Nikolsky sign (concern for SJS/TEN).
  • Look for signs of infection: oozing, honey-colored crusts, purulence, warmth, tenderness.
  • Check scalp (scale, plaques), nails (pitting, onycholysis), palms/soles (keratoderma), hair loss.
• Mucosae: oral, ocular, genital involvement.
• Lymph nodes: cervical, axillary, inguinal; size, tenderness, fixation.
• Organomegaly: liver, spleen.
• Edema, signs of volume depletion, signs of heart failure.
• Photographs of representative areas (with consent) for serial comparison.

4. Laboratory Studies

Obtain within first 24 hours (many immediately):

Baseline / diagnostic:

• CBC with differential
  • Eosinophilia → drug reaction/DRESS, atopy
  • Atypical lymphocytes, lymphocytosis → DRESS, CTCL, viral infection
• CMP (Na, K, Cl, CO₂, BUN, Cr, glucose, LFTs)
  • Evaluate for renal/hepatic involvement (DRESS; drug toxicity; dehydration).
• Albumin and total protein
  • Assess protein loss, nutritional status.
• CRP and/or ESR
  • Inflammatory burden; trend.
• LDH
  • Often elevated in CTCL/lymphoma or high inflammatory burden.
• Uric acid
  • Baseline if considering cyclosporine.
• Mg and Ca
  • Important with extensive barrier loss and for cyclosporine safety.
• Urinalysis
  • Renal involvement (DRESS, systemic disease).

Infection & immunosuppression screen (prior to systemic immunosuppressants/biologics):

• HIV 1/2 Ag/Ab.
• Hepatitis B: HBsAg, anti‑HBs, anti‑HBc (total or IgG).
• Hepatitis C Ab.
• TB screening: Quantiferon‑TB Gold or T‑Spot TB (ordered early; results may take time).
• Blood cultures x2 sets if febrile or hemodynamically unstable.
• Wound/skin cultures from exudative, pustular, or crusted lesions.

As indicated:

• Peripheral blood smear (look for Sézary cells, atypical lymphocytes).
• Flow cytometry of peripheral blood for T‑cell immunophenotype (CD4:CD8 ratio, loss of pan‑T markers) if CTCL suspected.
• Serum IgE if strong atopic history.
• ANA and other autoantibodies if systemic connective tissue disease is suspected.
• Ferritin if hyperinflammatory syndrome considered.

5. Imaging

Not routine; use if indicated:

• Chest X-ray: systemic symptoms, cough, or lymphadenopathy.
• CT chest/abdomen/pelvis or ultrasound of nodes: significant lymphadenopathy, B symptoms, markedly elevated LDH, or CTCL/other lymphoma concern.

6. Procedures

1. Skin biopsies (within first 24 hours)

   • 2–3 punch biopsies (4 mm), from:
     • Newer, inflamed erythematous area.
     • More evolved, scaly area.
   • Submit for H&E.
   • Obtain an additional perilesional biopsy for direct immunofluorescence (DIF) if:
     • Bullous disease suspected,
     • Prominent mucosal involvement, or
     • Autoimmune connective tissue disease is a consideration.

2. CTCL-specific studies (if suspicious features)

   • TCR gene rearrangement on tissue and peripheral blood.
   • Flow cytometry and Sézary cell count, as above.

3. Bedside tests as indicated

   • KOH prep from scale if tinea incognito possible.
   • Scabies scrapings if hyperkeratotic plaques, nail involvement, or institutional exposure.

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Treatment Plan

1. Immediate stabilization (0–2 hours and ongoing)

Temperature & environment

• Warm room (avoid drafts); warming blankets if hypothermic, but avoid overheating.
• Gentle, lukewarm bathing only; no harsh soaps.

Fluids & electrolytes

• Secure IV access (preferably two lines).
• Start isotonic IV fluids (e.g., normal saline or balanced crystalloid), titrated to:
  • BP, HR, capillary refill, and urine output (goal ≥0.5 mL/kg/hr).
• Correct Na, K, Mg, Ca abnormalities as they arise.

Medication reconciliation

• Immediately stop all nonessential and all newly started medications from the prior 2–8 weeks—especially:
  • Antibiotics, antiepileptics, allopurinol, sulfonamides, dapsone, minocycline, antiretrovirals, checkpoint inhibitors, NSAIDs.
• Document suspected culprits and list as “avoid/re-challenge only with specialist oversight.”

2. Universal supportive skin care

Topical barrier care

• Emollients:
  • Liberal petrolatum or thick, fragrance-free emollient over entire body every 2–4 hours (nurse-assisted whole-body application).
• Topical corticosteroids (unless SJS/TEN suspected):
  • Trunk/extremities: triamcinolone 0.1% ointment or equivalent mid–high potency, thin layer BID.
  • Face, intertriginous areas, genitals: hydrocortisone 2.5% cream or equivalent low potency BID.
• Wet wraps (24–72 hours if eczematous/very inflamed):
  • Apply topical steroid then emollient; cover with moist cotton layer then dry layer, especially over trunk and limbs.
• Scalp:
  • Mineral oil soaks; gentle removal of scale; mild tar or salicylic shampoos once stable (avoid aggressive debridement acutely).

Infection management

• Do not start systemic antibiotics empirically unless:
  • Clinical signs of infection (purulence, cellulitis, rapidly spreading erythema, systemic toxicity), or
  • Positive cultures plus compatible clinical picture.
• If needed, cover Staph aureus including MRSA per local resistance (e.g., IV vancomycin or oral doxy/clindamycin depending on severity; adjust to culture results).

3. Symptom control

• Pruritus:

  • Daytime: cetirizine 10 mg PO daily or fexofenadine 180 mg PO daily.
  • Night: hydroxyzine 25 mg PO qhs PRN (adjust dose for sedation).
  • If pruritus refractory: gabapentin 100–300 mg qhs, titrate every 2–3 days as needed and tolerated.

• Pain:

  • Acetaminophen up to 3–4 g/day (depending on liver status).
  • Avoid NSAIDs in the setting of volume depletion or renal risk.

4. Systemic anti-inflammatory / immunosuppressive therapy

Because the etiology is unknown initially, therapy should be effective yet safe in the undifferentiated setting and adjusted as clues emerge.

A. Empiric cyclosporine (if SJS/TEN not suspected and no major contraindications)

• Indications:

  • Severe, extensive erythroderma with suspected inflammatory dermatosis (psoriasis or eczema) or severe idiopathic erythroderma.
  • Rapid control needed to reduce systemic complications.

• Regimen:

  • Cyclosporine 3–5 mg/kg/day PO, divided BID (start at 3 mg/kg/day if moderate disease or renal concerns, higher end if fulminant and low comorbidity burden).
  • Baseline: blood pressure, serum creatinine, electrolytes (especially Mg, K), LFTs.
  • Monitoring:
    • BP and serum creatinine every 2–3 days initially.
    • Adjust dose or discontinue if >30% rise in creatinine from baseline or sustained hypertension.

• Avoid/Use caution:

  • Uncontrolled hypertension, significant baseline renal dysfunction, concomitant nephrotoxic drugs.

B. Systemic corticosteroids – only in selected scenarios

• Avoid if psoriasis is strongly suspected (history, nail changes, islands of sparing), due to risk of severe rebound or pustular transformation upon tapering.

• Consider a cautious short course only if:

  • Strong evidence for drug-induced hypersensitivity/DRESS or severe eczematous erythroderma, and psoriasis appears unlikely.

• Example regimen (if indicated):

  • Prednisone 0.5–1 mg/kg/day PO (e.g., 30–60 mg/day), with plan for slow taper over weeks in DRESS, or more rapid taper over 1–2 weeks in severe eczema once a safer long-term agent (e.g., cyclosporine, dupilumab) is established.

• Monitor:

  • BP, glucose, mood, infection risk; serial LFTs and renal function (especially in DRESS).

C. Therapies deferred initially

• Systemic retinoids (acitretin): may be useful in psoriatic erythroderma or PRP but slower onset; consider after partial stabilization and diagnosis is clearer.
• Methotrexate and biologics:
  • Typically deferred until etiology more defined and screening labs completed.
• Phototherapy:
  • Generally delayed until acute inflammation/infection controlled; also approach cautiously if CTCL suspected (sometimes used but ideally after diagnosis is established).

5. Etiology-directed branches (to activate as information emerges)

If DRESS / drug-induced erythroderma favored:

• Strong temporal relation to high-risk drug, facial edema, eosinophilia, LFT elevation, lymphadenopathy.
• Stop culprit drugs definitively.
• Initiate systemic steroids (as above) with slow taper; monitor for delayed organ injury (repeat LFTs, creatinine, thyroid tests, etc. per local protocol).

If psoriatic erythroderma favored:

• History of psoriasis, nail pitting, scalp involvement, islands of sparing, possible recent steroid withdrawal.
• Continue/optimize cyclosporine as first-line rapid agent.
• Avoid systemic corticosteroids.
• Once stable, plan transition to methotrexate or biologic (IL‑17/IL‑23 inhibitor or TNF‑α inhibitor) after TB/hepatitis screening.

If eczematous/atopic erythroderma favored:

• Atopy, intense pruritus, lichenification, flexural pattern.
• Maintain aggressive topical therapy + wet wraps.
• Short course cyclosporine for rapid control is reasonable.
• Consider short systemic steroid bridge only if necessary, with clear taper plan.
• Longer term: consider dupilumab once infection excluded and screening done.

If CTCL / Sézary syndrome suspected:

• Ensure multiple deep biopsies, TCR clonality, flow cytometry, Sézary cell count; early heme/oncology referral.
• Avoid prolonged or high-dose systemic steroids that may suppress or obscure histologic diagnosis.
• Focus on supportive care, antipruritic measures; initiate CTCL-specific therapies (photopheresis, retinoids, interferon, targeted agents) once diagnosis confirmed.

If scabies / crusted scabies suspected:

• Implement contact precautions.
• Permethrin 5% cream from neck down (include scalp in crusted scabies) on days 1, 2, then weekly x2.
• Oral ivermectin 200 µg/kg on days 1, 2, 8, 9, 15 (adjust per severity and guidelines).
• Treat close contacts; add keratolytics and manage secondary infection.

6. Prevention of complications

• VTE prophylaxis: low molecular weight heparin or equivalent per hospital protocol, unless contraindicated.
• Nutrition:
  • High-protein, high-calorie diet; early dietitian consult.
  • Monitor weight, albumin, and prealbumin if available; consider nutritional supplements.
• Cardiac & renal:
  • Monitor for tachycardia, high-output heart failure in severe cases; daily weights, I/O, creatinine.

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Patient Education

Tailor to patient’s level of understanding; key points to cover before discharge (and reinforce during stay):

1. Nature of condition

   • “Your entire skin is inflamed and peeling, which can affect your body’s ability to hold in fluids, regulate temperature, and fight infection. That is why we are treating this as an emergency and keeping you in the hospital.”

2. Possible causes and uncertainty

   • Multiple potential triggers (medications, psoriasis, eczema, immune or blood disorders).
   • It is common that the exact cause is not clear immediately; biopsies and blood tests plus watching how the rash evolves will help narrow this down.

3. Medications and drug avoidance

   • Importance of stopping suspected culprit drugs and avoiding them in the future.
   • List drugs that must be avoided and provide written information.

4. Treatment plan overview

   • Emollients and topical steroids to restore skin barrier and reduce inflammation.
   • Possible use of systemic agents such as cyclosporine or, in selected cases, prednisone, with explanation of benefits and side effects.
   • Need for frequent blood tests and blood pressure checks while on certain medications.

5. Skin care at home (for transition)

   • Daily or twice-daily full-body application of thick moisturizer.
   • Correct use of topical steroids (amount, locations, duration).
   • Avoid harsh soaps, hot showers, and scratching (keep nails short; use cotton gloves at night if needed).

6. Infection prevention

   • Signs of skin infection (increasing redness, warmth, pain, pus, streaking, fever).
   • Importance of hand hygiene and wound care.

7. Long-term management

   • Depending on eventual diagnosis (psoriasis, eczema, CTCL, etc.), there may be a need for ongoing systemic treatment and regular dermatology visits.
   • Adherence to follow-up and lab monitoring is essential for safety.

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Follow-up Schedule

Inpatient (daily):

• Vitals, pain, and pruritus assessment.
• Skin exam: BSA involved, erythema/scale severity, new erosions or blisters, signs of infection.
• I/O, daily weights.
• Labs:
  • CBC, CMP (including Cr, LFTs), and electrolytes at least every 24–48h initially, more often if unstable or on nephrotoxic/immunosuppressive therapy.
  • Specific monitoring of creatinine and BP every 2–3 days with cyclosporine.
• Reassess need for antibiotics, systemic immunosuppressants daily.
• Re-biopsy if diagnosis remains unclear after 1–2 weeks or new morphology emerges.

Milestones:

• 24 hours: Stabilized vitals; pruritus and pain beginning to improve; no hemodynamic deterioration.
• 48–72 hours:
  • Reduced erythema/scale by ~25% or at least no progression.
  • Lab trends stabilizing or improving (electrolytes, Cr, LFTs, inflammatory markers).
  • Preliminary pathology/lab data to refine diagnosis and adjust systemic therapy.

Discharge criteria:

• Hemodynamically stable, afebrile.
• Pain and pruritus controllable with oral meds.
• Skin clearly improving; patient able to apply emollients/topicals or has support.
• Initial diagnostic framework established (or at least leading differential with plan).
• Clear outpatient medication and monitoring plan in place.

Outpatient follow-up:

• Dermatology visit: within 3–7 days post-discharge (earlier if unstable or biopsy results expected).
• Review biopsy and lab results; refine diagnosis; adjust systemic therapy.
• If CTCL suspected/confirmed: coordinate with hematology/oncology; schedule staging and treatment planning.
• If psoriasis confirmed: transition from short-term cyclosporine to methotrexate or biologic; monitor labs (CBC/CMP every 1–2 weeks while adjusting, then monthly).
• If eczema confirmed: consider dupilumab or other steroid-sparing regimen; trigger avoidance; possible patch testing after 6–8 weeks.
• Monitoring on cyclosporine:
  • BP and creatinine 2x weekly initially, then weekly; aim to limit total course to ≤12 weeks.
• Vaccination & prevention:
  • Update non-live vaccines before long-term immunosuppression if possible; avoid live vaccines while on significant immunosuppression.

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Red Flags / When to Return Sooner

Patient should seek immediate medical attention (ED or urgent call to provider) if any of the following occur:

• Fever ≥38.5°C (101.3°F) or chills, especially with worsening skin pain, redness, or pus.
• Sudden worsening of rash, new blisters, skin sloughing, or significant mucosal erosions (eyes, mouth, genitals).
• Shortness of breath, chest pain, palpitations, or new leg swelling.
• Decreased urine output, dizziness, confusion, fainting episodes.
• Uncontrolled pain or itching despite medications.
• Yellowing of the eyes/skin, dark urine, severe abdominal pain (possible liver involvement).
• New lymph node enlargement, night sweats, or unexplained weight loss (possible lymphoma/CTCL progression).

This integrated plan prioritizes stabilization, early drug cessation, structured diagnostic workup, and cautious empiric therapy while preserving flexibility to pivot toward a specific etiology as data accumulate.