Causes of Erythema Nodosum in Pregnancy
Erythema nodosum in pregnancy is most commonly caused by infections (particularly streptococcal and coccidioidomycosis), hormonal changes related to pregnancy itself, inflammatory bowel disease, sarcoidosis, and drugs, though up to half of cases remain idiopathic.
Primary Etiologic Categories
Infectious Causes
Coccidioidomycosis is a critical infectious trigger, particularly in endemic areas (southwestern United States). Among pregnant women with coccidioidomycosis, erythema nodosum serves as a favorable prognostic marker—97% of pregnant patients with erythema nodosum recovered, compared to only 55% without it 1. Importantly, no cases of disseminated coccidioidomycosis occurred among 30 pregnant women who developed erythema nodosum, versus 11 cases of dissemination among 31 without this manifestation 1.
Streptococcal infections represent another well-documented infectious trigger. Elevated antistreptolysin-O (ASO) titers can confirm recent streptococcal infection, and treatment with antibiotics (10-14 days) is warranted when identified 2.
Histoplasmosis can also present with erythema nodosum as part of rheumatologic syndromes, appearing as an inflammatory response to the infection rather than the infection itself 3.
Hormonal Mechanisms
Pregnancy itself creates an optimal background for erythema nodosum development through hormonal mechanisms 4, 5, 6. The condition may represent:
- A hypersensitivity reaction to estrogens or progesterone
- An immune complex-mediated process
- A response to altered estrogen/progesterone ratios
The observation that lesions spontaneously resolve in the fifth month of pregnancy supports the hypothesis that specific hormone concentrations or ratios are critical 5. Cases have been documented where erythema nodosum recurred with each pregnancy and oral contraceptive use, disappearing when hormones were withdrawn 5, 6.
Inflammatory and Autoimmune Conditions
Inflammatory bowel disease (particularly ulcerative colitis) is an important cause. Diagnosis is made on clinical grounds, though skin biopsy may help in atypical cases 7. The condition typically parallels disease activity.
Sarcoidosis remains a recognized trigger, though less commonly documented in pregnancy-specific literature 4, 8.
Drug-Induced Causes
Multiple medications can trigger erythema nodosum during pregnancy, requiring careful medication history review 4, 8. Consider all recently initiated medications as potential triggers.
Idiopathic Cases
Up to 50% of erythema nodosum cases have no identifiable underlying cause 4, 8, making this the single most common "etiology" when all specific causes are excluded.
Diagnostic Approach
When evaluating erythema nodosum in pregnancy, systematically assess:
- Recent infections: Obtain throat culture, ASO titers, chest imaging if respiratory symptoms present, and consider coccidioidomycosis serology in endemic areas
- Medication history: Review all drugs initiated within the past several months
- Inflammatory disease symptoms: Assess for gastrointestinal symptoms (IBD), respiratory symptoms (sarcoidosis), or systemic manifestations
- Skin biopsy: Reserve for atypical presentations to confirm septal panniculitis 7
Critical Clinical Pearls
- In coccidioidomycosis-endemic areas, erythema nodosum is a positive prognostic sign indicating robust cellular immunity and dramatically reduced risk of dissemination 1, 9
- The condition is self-limiting in most cases, with lesions typically resolving spontaneously 4, 5
- Hormonal changes during pregnancy can both trigger and resolve erythema nodosum, with spontaneous resolution often occurring in the fifth month 5
- When streptococcal infection is identified or suspected, antibiotic treatment is warranted even if the primary infection has resolved 2
Management Implications
Treatment focuses on the underlying cause when identified. For symptomatic management during pregnancy, bed rest, elastic bandages, and supportive care are first-line 4. Systemic treatments must be carefully selected given pregnancy considerations, with NSAIDs contraindicated in the third trimester and corticosteroids reserved for severe cases requiring careful risk-benefit analysis 3, 4.