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Dermatologic Manifestations in Patients with Systemic Disease


Key features

  • ▪

    Because of the frequency of skin involvement in systemic diseases, cutaneous manifestations often prove helpful in establishing the correct diagnosis

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    Skin signs of systemic disease can be specific, e.g. cutaneous lupus, cutaneous sarcoidosis, in part because of associated histologic features, while others are best described as suggestive, e.g. pyoderma gangrenosum, acquired ichthyosis

  • ▪

    Cutaneous disease can serve as the initial manifestation of a systemic disorder, including an internal malignancy

Skin disease is often associated with internal manifestations , e.g. psoriatic arthritis, and there are many cutaneous disorders that are traditionally associated with systemic disease. For example, rheumatologic disorders frequently have skin manifestations, as do infectious diseases and endocrinopathies. When one examines many of the disorders that are discussed elsewhere in this text, it becomes clear that isolated dermatologic disease is relatively uncommon. A detailed review of all dermatologic signs of internal disease is beyond the scope of this chapter. Rather, representative disorders are discussed individually, while the remainder are reviewed via tables that contain information relevant to dermatologists. Disorders are grouped on the basis of affected organ systems.

Cutaneous Rheumatology

The spectrum of disorders traditionally considered to be cutaneous rheumatology includes: lupus erythematosus ( Ch. 41 ); dermatomyositis ( Ch. 42 ); systemic sclerosis ( Ch. 43 ); vasculitides ( Ch. 24 ); and miscellaneous disorders. Miscellaneous disorders usually include: rheumatoid arthritis ( Ch. 45 ), reactive arthritis (formerly Reiter disease) ( Ch. 8 ), psoriatic arthritis ( Ch. 8 ), Behçet disease ( Ch. 26 ), pyoderma gangrenosum ( Ch. 26 ), Sweet syndrome ( Ch. 26 ), bowel-associated dermatosis–arthritis syndrome ( Ch. 26 ), Kawasaki disease ( Ch. 81 ), relapsing polychondritis ( Ch. 45 ), and several of the autoinflammatory disorders (see Table 45.7 ).

Cutaneous conditions reported in patients with rheumatoid arthritis are summarized in Table 53.1 ( Figs 53.1–53.5 ) . Dermatologists should be particularly careful in this group of patients to couple laboratory evaluation with a comprehensive cutaneous examination, including all mucosal surfaces, nails, nail folds, and hair. Clinical criteria are published for the diagnosis of many of these disorders; dermatologists should be familiar with these criteria and incorporate them into a focused, thorough history, which includes relevant negatives. It is very helpful to consider the clinicopathologic basis and pathogenesis of cutaneous lesions. For example, patients with systemic lupus erythematosus can have different types of photodistributed lesions with an interface histopathology, e.g. discoid, subacute, poikilodermatous, and they have different implications with regard to systemic disease. Such lesions are also treated differently than those caused by vessel-based pathology, e.g. small or larger vessel vasculitis.

Table 53.1
Cutaneous manifestations of rheumatoid arthritis (RA).
DDx, differential diagnosis; EBV, Epstein–Barr virus; LE, lupus erythematosus; TNF, tumor necrosis factor.
CUTANEOUS MANIFESTATIONS OF RHEUMATOID ARTHRITIS
Condition Features
Palisading granulomas
Rheumatoid nodules

  • Seen in ~20% of RA patients, often associated with high-titer rheumatoid factor (RF)

  • Firm, semi-mobile papulonodules favoring periarticular locations (e.g. elbows; see Figs 24.6B & 45.5) and other sites of repetitive trauma or pressure (e.g. the sacral region if bedridden)

  • Histologically, central zone of eosinophilic fibrin surrounded by palisaded histiocytes

  • DDx: subcutaneous granuloma annulare, gouty tophi, synovial hyperplasia/cysts (softer, painful)

Interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic & granulomatous dermatitis (PNGD)
Neutrophilic dermatoses
Rheumatoid neutrophilic dermatitis (rheumatoid neutrophilic dermatosis)

  • Erythematous papules and plaques that may be vesiculated or crusted; favors extensor extremities

  • Unlike Sweet syndrome, not tender or associated with fevers and malaise

Sweet syndrome and pyoderma gangrenosum (PG) *
Neutrophilic lobular panniculitis

  • Tender red nodules favoring the lower legs; may ulcerate with purulent drainage

Vasculitis and vascular reactions
Bywaters lesions

  • Punctate purpuric papules on the distal digits due to cutaneous small vessel vasculitis ( Fig. 53.4 )

Rheumatoid vasculitis

  • Associated with long-standing (often “burnt out”) joint disease, high-titer RF, and mononeuritis multiplex; may also affect the eyes and internal organs

  • Cutaneous involvement is usually the first manifestation

    • -

      Small vessel vasculitis : purpuric macules and papules (see Fig. 24.6B )

    • -

      Medium-sized vessel vasculitis : nodules, ulcers, digital gangrene, livedo reticularis, atrophie blanche-like scars

  • Systemic disease requires aggressive immunosuppressive therapy

Intravascular/intralymphatic histiocytosis

  • Erythema, induration and papules in a reticular pattern overlying swollen joints, most often the elbows

Erythema elevatum diutinum

  • Firm, red to yellow-brown papulonodules and plaques, usually symmetrically distributed over joints and on extensor surfaces

  • Chronic cutaneous vasculitis, occasionally associated with RA

Complications of therapy for RA
NSAIDs

  • Pseudoporphyria ( Fig. 53.5 ), toxic epidermal necrolysis

Methotrexate

  • EBV-associated lymphoproliferative disease may involve the skin

Methotrexate ≫ TNF inhibitors

  • Accelerated rheumatoid nodulosis – sudden appearance of multiple papulonodules, especially on the hands (see Fig. 45.6 )

TNF inhibitors

  • Local injection site reactions, urticaria, urticarial eruptions, vasculitis, IGD, cutaneous LE, psoriasiform eruptions, palmoplantar pustulosis, dermatomyositis

* “PG-like” leg ulcers are a feature of Felty syndrome, which is characterized by the triad of neutropenia, splenomegaly, and RA; Felty syndrome may be associated with T-cell large granular lymphocyte leukemia.

Fig. 53.1, Rheumatoid papules.

Fig. 53.2, Annular variant of interstitial granulomatous dermatitis (IGD).

Fig. 53.3, Superficial ulcerating rheumatoid necrobiosis.

Fig. 53.4, Bywaters lesions.

Fig. 53.5, Pseudoporphyria in a patient with rheumatoid arthritis.

Sjögren syndrome is an autoimmune disorder that is characterized by keratoconjunctivitis sicca and xerostomia (see Table 45.4 ). In primary Sjögren syndrome, vascular inflammation within the skin (e.g. small vessel vasculitis, hypergammaglobulinemic purpura) can occur even before the clinical diagnosis of Sjögren syndrome has been established. Some patients from the Far East, including Japan and the Philippines, have been described with “annular erythema of Sjögren syndrome”. There is ongoing debate as to whether this disorder is unique to Sjögren syndrome or if it is, in fact, a form of subacute cutaneous lupus erythematosus . Secondary Sjögren syndrome occurs in patients with other rheumatologic diseases, including rheumatoid arthritis, dermatomyositis and systemic sclerosis. It is important to remember that the diagnosis of Sjögren syndrome is one of exclusion, and that other conditions can cause xerostomia/xerophthalmia, including chronic GVHD, sarcoidosis, primary systemic amyloidosis, hepatitis C viral infection, and HIV disease.

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