INFLAMMATORY AND IMMUNE-MEDIATED SKIN DISORDERS

Erythema Nodosum

Classification: Panniculitis in which inflammation is concentrated primarily in the connective-tissue septa of subcutaneous fat (Pincus & McCalmont, 2019).

Key diagnostic discriminator: Crops of tender, poorly demarcated red or red-brown subcutaneous nodules occur most often on the anterior lower legs and evolve into bruise-like lesions (Pincus & McCalmont, 2019).

Clinical priority: A prolonged course should prompt evaluation for persistent infection or another continuing precipitating condition (Pincus & McCalmont, 2019).

Etiology and risk factors

  • Erythema nodosum represents a common inflammatory response to infection, medication, hormones including pregnancy, or inflammatory disease (Pincus & McCalmont, 2019).
  • Recognized associations include streptococcal pharyngitis, sulfonamide-containing drugs, estrogen-containing oral contraceptives, inflammatory bowel disease, and sarcoidosis (Pincus & McCalmont, 2019).

Pathophysiology

  • The inflammatory response occurs primarily in the septal compartment of subcutaneous fat and includes lymphocytes, histiocytes, neutrophils, and eosinophils (Pincus & McCalmont, 2019).
  • The favored mechanism is a delayed-type hypersensitivity response localized to septal fat. Immune-complex deposition has not been demonstrated in lesions (Pincus & McCalmont, 2019).

Clinical manifestations

  • Tender deep red or red-brown nodules usually involve the anterior shins but can occur on the thighs, extensor forearms, or, rarely, the trunk (Pincus & McCalmont, 2019).
  • Lesions have indistinct borders and become bruise-like as they age. Fever, constitutional symptoms, and arthralgias may accompany the eruption (Pincus & McCalmont, 2019).
  • The eruption usually lasts several weeks to several months and may continue in crops while the precipitating stimulus remains present (Pincus & McCalmont, 2019).

Findings that argue against or redirect

  • A superficial eruption dominated by scale, vesicles, or epidermal change does not fit the deep subcutaneous pattern of erythema nodosum (Gohara et al., 2012; Pincus & McCalmont, 2019).
  • Sharply demarcated or ulcerating nodules should prompt consideration of another form of panniculitis or a different nodular disorder (Gohara et al., 2012; Pincus & McCalmont, 2019).

Diagnostic evaluation

  • Recognize the characteristic tender subcutaneous nodules and evaluate for an associated infection, medication, hormonal exposure, or inflammatory disease (Gohara et al., 2012; Pincus & McCalmont, 2019).
  • When tissue is examined, the specimen must include subcutaneous fat so the septal distribution of inflammation can be assessed (Gohara et al., 2012; Pincus & McCalmont, 2019).

Expected diagnostic and laboratory findings

  • Histology shows thickened, inflamed septa with lymphocytes, histiocytes, neutrophils, eosinophils, and diagnostically useful multinucleated histiocytes (Pincus & McCalmont, 2019).
  • The inflammatory process is mainly septal, although inflammation and limited fat necrosis can extend to the edges of adjacent lobules (Pincus & McCalmont, 2019).

Differential diagnosis

  • Other forms of panniculitis: distinguished by whether inflammation is primarily septal or lobular and by the composition of the infiltrate (Gohara et al., 2012; Pincus & McCalmont, 2019).
  • Cellulitis and other inflammatory nodules: distinguished through depth, distribution, lesion borders, and the overall clinical pattern (Gohara et al., 2012; Pincus & McCalmont, 2019).
  • Sarcoidosis: erythema nodosum can be a presenting sign, so associated systemic findings should be considered (Gohara et al., 2012; Pincus & McCalmont, 2019).

Treatment and management

  • Address an identifiable precipitating condition. Streptococcus-associated lesions generally resolve within several weeks after successful antibiotic treatment of the primary infection (Pincus & McCalmont, 2019).
  • Continued or recurrent crops indicate that the precipitating stimulus may still be present and warrant further etiologic evaluation (Pincus & McCalmont, 2019).

Additional complications and red flags

  • Persistence beyond the expected course can indicate an untreated infection or another continuing underlying cause (Pincus & McCalmont, 2019).

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References

Gohara, M. A., Schaffer, J. V., Abbasi, N. R., Kingsley, M. M., Sheehan, J. M., & Arndt, K. A. (2012). Inflammatory dermatoses (rashes). In M. C. Henderson, L. M. Tierney, Jr., & G. W. Smetana (Eds.), The patient history: An evidence-based approach to differential diagnosis (2nd ed.). McGraw-Hill.

Pincus, L. B., & McCalmont, T. H. (2019). Diseases of the skin. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.