Erythema Nodosum: A Clue to Underlying Disease for PLAB 2

Ann Augustin
Jun 5
3 min read

Updated: Jun 26

Erythema nodosum (EN) is a form of panniculitis — inflammation of the subcutaneous fat (panniculus). It appears as tender, red nodules, usually on the shins, and often signals an underlying systemic condition.

🔍 What Is the Panniculus?

The panniculus (or hypodermis) is the fat layer beneath the dermis. It insulates, protects, and stores energy. When this layer becomes inflamed, it results in panniculitis — of which EN is the most common type.

🚨 Causes of Erythema Nodosum

EN is a reaction pattern, not a disease itself. It may be caused by:

Category	Examples
Infections	Streptococcal throat infection (most common), TB, Yersinia, Salmonella, EBV
Autoimmune	Sarcoidosis, inflammatory bowel disease (IBD), Behçet’s disease
Drugs	Oral contraceptives, sulfonamides, penicillin, NSAIDs
Pregnancy	Especially during the first trimester due to hormonal changes
Malignancy (rare)	Lymphoma, leukemia
Idiopathic	No clear cause found in up to 50% of cases

🌡️ Systemic Symptoms of EN

EN is often accompanied by:

Low-grade fever
Malaise, fatigue
Joint pain, especially in ankles
Sometimes sore throat, weight loss, or GI symptoms — depending on the cause

🌍 Where Can EN Occur?

EN usually affects:

Shins (most common)
Thighs, forearms, upper arms (less common)
It can occur on both legs or multiple sites at once, but not typically on the face or trunk

🤰 EN in Pregnancy

Triggered by high estrogen and progesterone
Occurs most often in the first trimester
Usually self-limiting and resolves within weeks
Treated with paracetamol, rest, and supportive care (NSAIDs are avoided in later pregnancy)

🧬 Pathophysiology

EN is a Type IV hypersensitivity reaction, where the immune system reacts to a trigger (infection, drug, etc.) and causes septal panniculitis without vasculitis — inflammation in the fat layer between lobules.

🩺 EN and Inflammatory Bowel Disease (IBD)

EN can occur with both Crohn’s disease and ulcerative colitis, but is more common in Crohn’s. It often appears during active disease flares.

IBD Symptoms That May Accompany EN:

Diarrhea, abdominal pain
Fever, fatigue
Weight loss
Joint pain
Breathlessness may occur due to:
- Anemia (very common in IBD)
- Pulmonary embolism (IBD is a hypercoagulable state)
- Drug-related lung toxicity (e.g., sulfasalazine)

🔍 Diagnostic Workup for EN

CBC, ESR/CRP
Throat swab, ASO titre (strep)
Mantoux/IGRA (TB)
Chest X-ray (TB, sarcoidosis)
Colonoscopy (if IBD suspected)
Medication review and pregnancy test when relevant

💊 Common Medications Associated with Erythema Nodosum

Drug Class	Examples	Notes
Antibiotics	🔹 Sulfonamides (e.g., sulfamethoxazole) 🔹 Penicillins (e.g., amoxicillin) 🔹 Tetracyclines	Among the most frequently reported drug-induced causes
Oral Contraceptive Pills	Estrogen-containing OCPs	Hormonal modulation may trigger EN, especially early in use
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)	Ibuprofen, naproxen	Can trigger hypersensitivity reactions
Anti-TB medications	Streptomycin, rifampin (rarely)	Important in patients receiving TB therapy
Other antimicrobials	Minocycline, erythromycin	Minocycline-induced EN reported in acne treatment
Biologics	TNF-α inhibitors (in rare paradoxical reactions)	EN may develop as a side effect even while treating IBD
Anti-thyroid drugs	Propylthiouracil	Rare, immune-mediated

🧠 Mechanism

EN caused by medications is generally a delayed-type (Type IV) hypersensitivity reaction, where the drug or its metabolites act as antigens.
Inflammatory cells (especially T-cells) infiltrate the subcutaneous septa, leading to panniculitis.

⏳ Timing

Typically appears 1–3 weeks after starting the medication
May appear sooner in sensitized individuals (e.g., re-exposure)

🩺 Management

Stop the suspected drug
Symptomatic treatment:
- Leg elevation, rest
- Paracetamol for pain
- Avoid NSAIDs if they’re the suspected trigger
EN usually resolves within 2–6 weeks after withdrawal of the offending medication

💊 Treatment Overview

Approach	Plan
Symptomatic relief	Rest, leg elevation, paracetamol (NSAIDs if not contraindicated)
Treat cause	Antibiotics for strep, steroids for IBD or sarcoidosis, stop culprit drug
Persistent cases	May require colchicine, potassium iodide, or corticosteroids

🧷 Summary Table

Cause	EN Features	Management
Strep infection	Fever, sore throat, ↑ASO titre	Penicillin or amoxicillin
Crohn’s/UC	GI symptoms, joint pain	Treat IBD flare; EN improves in parallel
Pregnancy	Occurs in first trimester	Supportive only, resolves spontaneously
Behçet’s	Oral/genital ulcers, eye symptoms	Immunosuppressants, colchicine
TB	Cough, weight loss, positive Mantoux	Full anti-TB therapy
Sarcoidosis	Hilar lymphadenopathy, joint pain	Observation or steroids

🧠 Final Thoughts

Erythema nodosum is a clinical clue, not a diagnosis. It usually resolves on its own, but it’s essential to identify and treat the underlying condition to prevent recurrence or systemic complications.

📚 References