12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses

Cutaneous disorders represent a significant proportion of internal medicine ambulatory and inpatient consultations. A rigorous understanding of epidermal barrier biology, autoimmune effector pathways, clinical differentiation between infectious and inflammatory mimickers, and evidence-based topical and biologic pharmacotherapies is essential for the ABIM certification exam.

1. Inflammatory Dermatoses

Atopic Dermatitis (Eczema)

• Pathophysiology: A chronic, pruritic, relapsing inflammatory skin disease driven by a complex interplay of epidermal barrier disruption, immune dysregulation (T-helper 2 [Th2] cell-skewed immune response with excess interleukin-4 [IL-4] and interleukin-13 [IL-13]), and environmental triggers. Loss-of-function mutations in the filaggrin (FLG) gene impair stratum corneum integrity, leading to increased transepidermal water loss (TEWL) and enhanced penetration of cutaneous allergens and microbes.
• Clinical Presentation:
  • Morphology: Intensely pruritic, erythematous papules and patches that coalesce into scaly, excoriated plaques with lichenification (thickened skin with exaggerated markings from chronic rubbing).
  • Distribution: Strongly age-dependent. In adolescents and adults, lesions classically involve flexural surfaces (antecubital and popliteal fossae, anterior neck, dorsal hands and wrists). In infants, lesions predominantly affect the face, scalp, and extensor surfaces of extremities, sparing the diaper area.
  • Atopic Triad ("Allergic March"): Personal or family history of atopic dermatitis, allergic rhinitis, and asthma.
  • Complications: Increased susceptibility to cutaneous viral infections, most notably Eczema Herpeticum (Kaposi varicelliform eruption) caused by Herpes Simplex Virus (HSV-1/2) superinfection. Eczema herpeticum presents as sudden eruption of monomorphic, punched-out, umbilicated vesicles and erosions over pre-existing eczematous skin accompanied by high fever and lymphadenopathy; it is a dermatologic emergency requiring prompt systemic oral or IV Acyclovir.
• Stepwise Management Strategy:
  1. Foundational Skin Care (All Patients): Lukewarm, brief baths (5-10 minutes); mild fragrance-free non-soap synthetic cleansers; immediate application (within 3 minutes) of thick ceramide-containing emollients/ointments to trap cutaneous moisture; avoidance of harsh detergents and known contact allergens.
  2. First-Line Acute Flare Therapy: Topical Corticosteroids (TCS):
     • Face, eyelids, neck, and intertriginous areas: Low-potency TCS (e.g., Hydrocortisone 1% to 2.5%, Desonide 0.05% cream) to prevent cutaneous atrophy, telangiectasias, striae, and glaucoma/cataracts.
     • Trunk and extremities: Medium-to-high potency TCS (e.g., Triamcinolone acetonide 0.1%, Betamethasone dipropionate 0.05% cream/ointment) applied once to twice daily during active flares, then tapered.
  3. Steroid-Sparing Topicals (Maintenance & Sensitive Areas):
     • Topical Calcineurin Inhibitors (TCIs): Tacrolimus 0.03%-0.1% ointment or Pimecrolimus 1% cream. Inhibit T-cell activation by blocking calcineurin phosphatase. Excellent for facial, periorbital, and genital eczema without risk of skin atrophy.
     • Topical PDE-4 Inhibitor: Crisaborole 2% ointment (reduces intracellular cAMP degradation and downstream cytokine release).
     • Topical JAK Inhibitor: Ruxolitinib 1.5% cream (blocks JAK1/JAK2 signaling).
  4. Moderate-to-Severe Refractory Disease:
     • Phototherapy: Narrowband Ultraviolet B (NB-UVB).
     • Targeted Biologics: Dupilumab (human monoclonal antibody directed against the IL-4 receptor alpha [IL-4Rα] subunit, dual-inhibiting both IL-4 and IL-13 signaling; administered as 600 mg SC loading dose followed by 300 mg SC every 2 weeks). Highly effective with favorable safety; key adverse effect is allergic conjunctivitis and blepharitis. Tralokinumab (anti-IL-13 antibody).
     • Oral JAK Inhibitors: Upadacitinib or Abrocitinib (rapid onset of pruritus relief for severe refractory disease; requires monitoring for cytopenias, lipid elevations, and thrombosis risks).

Psoriasis Vulgaris

• Pathophysiology: Autoimmune, polygenic inflammatory disorder mediated by the IL-23 / Th17 / IL-17 cytokine axis. Antigen-presenting dendritic cells produce IL-23, which stimulates Th17 lymphocytes to secrete IL-17A, IL-17F, and IL-22. These cytokines drive marked keratinocyte hyperproliferation (epidermal transit time shortened from 28 days to 3-5 days), parakeratosis (retention of nuclei in stratum corneum), and dermal microvascular elongation.
• Clinical Subtypes & Features:
  • Chronic Plaque Psoriasis (Psoriasis vulgaris, ~85-90%): Well-demarcated, symmetrically distributed, erythematous plaques covered with coarse, silvery-white micaceous scales located over extensor surfaces (elbows, knees, scalp, lumbosacral region, umbilicus, gluteal cleft).
  • Classic Physical Exam Signs:
    • Auspitz Sign: Pinpoint bleeding when silvery scales are scraped off or removed, resulting from exposed and ruptured dilated dermal papillary capillaries beneath the thinned suprapapillary epidermal plates.
    • Koebner Phenomenon (Isomorphic Response): Development of new psoriatic plaques at sites of mechanical trauma, excoriation, or surgical incisions (shared with lichen planus and vitiligo).
  • Psoriatic Nail Disease (>50% of patients): Pitting (punctate depressions in nail plate), "oil-drop" or "salmon patch" subungual discoloration, subungual hyperkeratosis, and onycholysis (distal detachment of nail plate). Nail involvement strongly correlates with concomitant Psoriatic Arthritis (PsA).
  • Guttate Psoriasis: Acute, eruptive onset of hundreds of small (2-10 mm) "drop-like" erythematous scaly papules and plaques over the trunk and proximal extremities, classically arising 1 to 3 weeks following Streptococcus pyogenes (Group A Strep) pharyngitis in children and young adults. Often self-limiting or responsive to phototherapy and topical corticosteroids.
  • Inverse (Intertriginous) Psoriasis: Smooth, glistening, deep-red plaques without scales located within skin folds (axillae, inframammary, groin, perineal, and intergluteal clefts). Easily mistaken for Candida intertrigo or tinea cruris (distinguished by sharp borders and absence of satellite pustules).
  • Pustular & Erythrodermic Psoriasis: Severe, life-threatening variants. Generalized pustular psoriasis (GPP / von Zumbusch) features widespread sterile pustules on fiery red skin with high fever and leukocytosis.
• Stepwise Management Strategy:
  1. Localized Mild-to-Moderate Disease (<5-10% Body Surface Area [BSA]):
     • First-Line: High-potency Topical Corticosteroid (e.g., Clobetasol propionate 0.05%, Betamethasone dipropionate 0.05%) PLUS a Topical Vitamin D3 Analog (Calcipotriene 0.005% or Calcitriol 3 mcg/g). Combination therapy provides synergistic efficacy while mitigating corticosteroid-induced epidermal atrophy.
     • Topical Retinoids (Tazarotene 0.05-0.1%): Normalizes keratinocyte differentiation; best used in combination with TCS to reduce local irritation.
     • Topical Calcineurin Inhibitors (Tacrolimus/Pimecrolimus): Preferred for facial and inverse intertriginous psoriasis.
  2. Moderate-to-Severe Disease (>10% BSA, Psoriatic Arthritis, or High-Impact Areas [hands, feet, scalp, genitals]):
     • Phototherapy: Narrowband UVB (NB-UVB) 3 times weekly.
     • Oral Systemic Agents:
       • Methotrexate (7.5-25 mg PO/SC once weekly + daily Folic acid 1 mg): Inactivates dihydrofolate reductase; effective for cutaneous psoriasis and psoriatic arthritis. Monitor CBC (myelosuppression), LFTs (hepatotoxicity/cirrhosis), and pulmonary symptoms.
       • Apremilast (30 mg PO BID): Oral phosphodiesterase-4 (PDE-4) inhibitor increasing intracellular cAMP. No routine laboratory monitoring required; common adverse effects are diarrhea, nausea, headache, weight loss, and depression.
       • Acitretin: Oral retinoid; highly teratogenic (pregnancy contraindicated during and for 3 years post-discontinuation; avoid alcohol which converts acitretin to etretinate).
     • Biologic Therapies (Standard First-Line for Severe Disease & PsA):
       • Anti-TNF-alpha agents: Adalimumab, Infliximab, Etanercept, Certolizumab pegol (screen with QuantiFERON-TB and HBV panel prior to initiation).
       • Anti-IL-17A inhibitors: Secukinumab, Ixekizumab, Bimekizumab (dual IL-17A/F inhibitor). Rapid, profound plaque clearance; risk of mucocutaneous candidiasis and exacerbation of inflammatory bowel disease (contraindicated in active Crohn's disease).
       • Anti-IL-23 (p19 subunit) inhibitors: Guselkumab, Risankizumab, Tildrakizumab. High durability, superior PASI-90/100 clearance rates, administered every 8-12 weeks.
       • Anti-IL-12/23 (p40 subunit) inhibitor: Ustekinumab.

ABIM Board Pearl — Systemic Corticosteroids Contraindication: NEVER treat psoriasis flares with systemic oral corticosteroids (e.g., oral Prednisone or Medrol dose pack). Although oral steroids produce rapid initial improvement, tapering or discontinuing them triggers severe, life-threatening rebound generalized pustular psoriasis (GPP) or erythrodermic psoriasis with high morbidity and mortality.