Skin in Rheumatology and Immunology

1. Systemic Lupus Erythematosus (SLE)

A. Acute Cutaneous LE (ACLE)

• Malar ("butterfly") rash - erythematous, macular or raised, pruritic/painful, follows a malar distribution and spares the nasolabial folds (photoprotected region). Fluctuates with disease activity and lasts days to weeks.
• Generalized ACLE - widespread photosensitive erythema that may simulate toxic epidermal necrolysis in severe cases.

B. Subacute Cutaneous LE (SCLE)

• Widespread, nonscarring, nonindurated, photosensitive lesions.
• Start as erythematous papules/macules and evolve into:
  • Papulosquamous form (resembles psoriasis or lichen planus)
  • Annular/polycyclic form
• Strongly associated with anti-Ro (SSA) antibodies (up to 90% of SCLE). SCLE is also seen in Sjögren syndrome and RA with anti-SSA positivity.

C. Chronic Cutaneous LE (CCLE)

• Discoid LE (DLE) - most common chronic form. Erythematous plaques with thick adherent scale, follicular plugging, central hypopigmentation, and ultimately scarring + permanent alopecia when on the scalp.
• Lupus profundus (panniculitis) - firm deep subcutaneous nodules from lobular panniculitis. Overlying epidermis may be normal or show DLE changes.
• Bullous SLE - subepidermal bullae with neutrophilic infiltrate in dermal papillae (rare).
• Other chronic forms: chilblain lupus, tumid lupus, hypertrophic CLE.

D. Non-specific SLE skin signs

• Livedo reticularis, Raynaud's phenomenon, oral/nasal ulcers, hair thinning, photosensitivity.

E. Histopathology and Immunopathology

• Liquefactive (vacuolar) degeneration of the basal cell layer, fibrinoid necrosis, and perivascular/perifollicular T-cell infiltrate.
• Lupus band test - immunofluorescence demonstrates IgG, IgA, IgM + complement deposits at the dermal-epidermal junction (DEJ). Positive in both lesional AND non-lesional sun-exposed skin in active SLE. Can also be positive in RA, Sjögren, DM, and SSc.

2. Dermatomyositis (DM)

Pathognomonic signs

Highly specific signs

• Linear extensor erythema - over extensor joint surfaces.
• V-sign - photosensitive rash over the anterior neck and upper chest.
• Shawl sign - erythema over the upper back and shoulders.
• Holster sign - erythema over the hips and thighs.

Periungual changes

• Nailfold telangiectasias, periungual erythema, cuticular overgrowth, digital ulceration.

Other skin features

• Mechanic's hands (hyperkeratotic fissuring of the lateral fingers), panniculitis, livedo reticularis, nonscarring alopecia, poikiloderma (hypo/hyperpigmentation in late disease), pruritus (often severe).

Key differential - DM rash affects the knuckles but spares the phalanges, whereas SLE rash affects the phalanges but spares the knuckles.

In Juvenile DM (JDM)

• Gottron's papules and heliotrope are the hallmarks.
• Calcinosis (in 40%+) and ulcerative skin lesions - more common in JDM than adult DM. Ulcerative lesions herald systemic vasculopathy.
• Nailfold capillaroscopy shows dilated, abnormally shaped capillaries correlating with disease duration and severity.

3. Systemic Sclerosis (SSc / Scleroderma)

Skin Fibrosis

• Begins with edema and pruritus in early diffuse disease, progressing to fibrosis.
• Histology: dermal edema → mononuclear perivascular infiltrates → markedly increased collagen deposition in the reticular dermis → loss of hair follicles, sweat glands, and the intradermal white adipose layer.
• Myofibroblasts (α-SMA positive) are central to fibrosis.
• Late stage: acellular dermis with compact hyalinized collagen, loss of rete pegs, effacement of dermal-epidermal ridges.
• Modified Rodnan Skin Score (mRSS) is used clinically to grade skin thickness.
• Diffuse cutaneous SSc (dcSSc): proximal limb + trunk skin involvement; tends to improve over 3-5 years.
• Limited cutaneous SSc (lcSSc): restricted to face, neck, and extremities (CREST features).

Vascular Skin Changes

• Raynaud's phenomenon - triphasic color change (white/blue/red) in response to cold.
• Telangiectasias - classical palmar/facial lesions and serpiginous patterns. Increasing telangiectasia predicts pulmonary arterial hypertension.
• Rarefaction of dermal capillaries → chronic hypoxia → VEGF upregulation.
• Pruritus - prominent in early dcSSc; also occurs in late disease with skin dryness.

4. Psoriatic Arthritis (PsA) and Psoriasis

• 84% of PsA patients develop skin psoriasis before joint disease (typically 7-10 years before joint involvement).
• Up to 30% of psoriasis patients develop PsA.
• Higher risk psoriasis phenotypes for PsA development: nail disease, scalp, intergluteal, and inverse/flexural psoriasis. Obesity also increases risk.
• No direct correlation exists between extent of skin disease and extent of joint involvement.
• Nails: 60-80% of PsA patients have nail involvement (vs 20-40% in uncomplicated psoriasis). Nail-joint anatomical connection via Sharpey fibers to the distal phalanx underpins this association. Nail changes often precede joint involvement by only 1-2 years.

Immunopathology of psoriatic skin

• IL-23 → Th17 differentiation → IL-17A + TNF → keratinocyte hyperproliferation.
• Epidermal hyperplasia, mononuclear leukocytes in papillary dermis, neutrophils in the stratum corneum, increased dendritic cells (producing TNF, IL-12, IL-23).
• CD8+ T cells predominate in the epidermis; CD4+/CD8+ mix in the dermis.
• Prominent vascular changes with growth and dilation of superficial vessels (distinctive from RA synovium).

5. Rheumatoid Arthritis (RA)

Vasculitis-related skin manifestations

Nonspecific and associated skin disorders in RA

• Pyoderma gangrenosum (PG) - painful ulcer with undermined hemorrhagic borders (see image below). Histology shows neutrophilic infiltrate and small abscesses. Not directly correlated with RA course. DD includes venous/arterial ulcers, antiphospholipid syndrome, vasculitis.
• Palisaded neutrophilic and granulomatous dermatitis
• Interstitial granulomatous dermatitis
• Atrophic/fragile and transparent skin
• Palmar erythema, periungual erythema
• Splinter hemorrhages, nailfold thromboses
• Erythema nodosum, erythema multiforme, urticaria
• Alopecia areata, vitiligo
• Yellow nail syndrome

6. Sjögren Syndrome

• Most common dermatologic feature: xerosis (dry skin), eyelid dermatitis, angular cheilitis.
• Annular erythema - three types:
  • Type I: donut-ring erythema with elevated border (specific to primary Sjögren's, mainly Asian populations)
  • Type II: SCLE-like polycyclic scaled erythema
  • Type III: papular insect bite-like erythema
  • Histology: deep perivascular lymphocytic infiltrate WITHOUT the epidermal changes of lupus.
• Cutaneous vasculitis: most common form is palpable purpura of the lower extremities. Associated with anti-Ro/SS-A and anti-La/SS-B antibodies, cryoglobulins (~50%), and elevated RF.
• Cutaneous vasculitis predicts extraglandular manifestations: arthritis, peripheral neuropathy, Raynaud's.

7. Cutaneous Vasculitis in Rheumatic Disease

Vessel size and depth correlation

• Small vessels (<50 µm): capillaries, postcapillary venules - in the papillary dermis → IgA vasculitis (HSP), cutaneous leukocytoclastic angiitis (CLA), mixed cryoglobulinemia, CTD/rheumatoid vasculitis, ANCA vasculitis.
• Medium vessels (50-150 µm): in the reticular dermis/subcutaneous junction → PAN.

Key skin manifestation: Palpable purpura

• Palpable purpura = synonymous with small vessel vasculitis - the most common cutaneous finding in immune complex-mediated vasculitis.
• Results from erythrocyte extravasation through damaged vessel walls.
• Does not blanch on pressure (unlike reactive hyperemia).
• Other forms: vesicles, pustules, urticaria, superficial ulcerations, macules/patches, splinter hemorrhages.

Summary Table: Skin Findings by Disease

Key Immunological Mechanisms

• Firestein & Kelley's Textbook of Rheumatology, 2-Volume Set (2023)
• Rheumatology, 2-Volume Set (Elsevier, 2022)