List: Causes of Erythema Nodosum

TL;DR

List: Causes of Erythema Nodosum is a favourite MRCP Part 1 revision topic because it links dermatology, infectious diseases, rheumatology, gastroenterology and pharmacology. Erythema nodosum is a septal panniculitis that commonly reflects an underlying systemic disorder rather than a primary skin disease. Remember the major infectious, inflammatory, drug-related and pregnancy-associated causes, as exam questions frequently test these associations.

Why this matters

Erythema nodosum (EN) is the most common form of panniculitis and is an important systemic clue in clinical medicine. Rather than diagnosing the skin lesion alone, MRCP Part 1 expects candidates to recognise the diseases associated with it and understand the underlying immune mechanisms.

Typical examination questions present a patient with:

• Tender red nodules over the shins

• Fever or arthralgia

• A history suggesting infection, inflammatory disease or medication exposure

The correct answer often depends on identifying the underlying diagnosis instead of focusing solely on the dermatological appearance.

For a complete revision pathway, start with the MRCP Part 1 overview before testing yourself using the Free MRCP MCQs.

What is erythema nodosum?

Erythema nodosum is an acute inflammatory disorder of subcutaneous fat, specifically a septal panniculitis without vasculitis.

Classical features

• Painful, tender nodules

• Usually bilateral

• Located on the anterior shins

• Lesions evolve from bright red to bruise-like colours

• Heal without ulceration or scarring

• Often accompanied by fever, malaise and arthralgia

These clinical findings should immediately prompt a search for an underlying systemic disorder.

High-yield causes of erythema nodosum

The easiest way to remember causes is by category.

Category	High-yield examples	MRCP importance
Streptococcal infection	Recent pharyngitis	Very common
Tuberculosis	Pulmonary TB	Classic association
Sarcoidosis	Löfgren syndrome	Extremely high yield
Inflammatory bowel disease	Crohn's disease, ulcerative colitis	Frequently tested
Drugs	Sulfonamides, oral contraceptives, penicillins	Common exam theme
Pregnancy	Especially first trimester	Moderate yield
Fungal infections	Histoplasmosis, Coccidioidomycosis	Important for travel history
Malignancy	Lymphoma, leukaemia	Less common but examinable
Behçet disease	Systemic vasculitis	Occasional question
Idiopathic	No identifiable cause	Up to half of cases

The 10 causes every MRCP candidate should know

1. Streptococcal infection

Recent Group A Streptococcus pharyngitis is among the commonest causes.

Clinical clues:

• Sore throat 2–3 weeks earlier

• Raised ASO titre

• Fever

• Tender cervical lymph nodes

2. Sarcoidosis

One of the highest-yield associations.

Remember Löfgren syndrome:

• Erythema nodosum

• Bilateral hilar lymphadenopathy

• Polyarthritis (especially ankles)

This combination is frequently tested because it predicts a favourable prognosis.

3. Tuberculosis

Always consider tuberculosis in endemic areas or immunocompromised patients.

Clues include:

• Chronic cough

• Weight loss

• Night sweats

• Positive interferon-gamma release assay or Mantoux test

4. Inflammatory bowel disease

Both:

• Crohn's disease

• Ulcerative colitis

can produce erythema nodosum as an extra-intestinal manifestation.

Skin disease often parallels bowel disease activity.

5. Drug-induced erythema nodosum

Frequently implicated medications include:

• Sulfonamides

• Penicillins

• Oral contraceptive pills

• Bromides

• Iodides

Always ask about recently started medications.

6. Pregnancy

Pregnancy produces immune and hormonal changes that may trigger erythema nodosum.

Most cases occur during:

• First trimester

Management is usually supportive.

7. Fungal infections

Important travel-related causes include:

• Histoplasmosis

• Coccidioidomycosis

• Blastomycosis

Travel history is a valuable examination clue.

8. Behçet disease

Features include:

• Oral ulcers

• Genital ulcers

• Uveitis

• Erythema nodosum-like lesions

9. Malignancy

Although uncommon, consider:

• Hodgkin lymphoma

• Non-Hodgkin lymphoma

• Leukaemia

Persistent or unexplained erythema nodosum warrants further evaluation.

10. Idiopathic disease

Approximately one-third to one-half of patients have no identifiable cause despite investigation.

The five most tested subtopics

1. Sarcoidosis

Know Löfgren syndrome completely.

2. Streptococcal infection

Understand the typical delay after pharyngitis.

3. Inflammatory bowel disease

Differentiate erythema nodosum from pyoderma gangrenosum.

4. Drug-induced disease

Identify oral contraceptives and sulfonamides as classic causes.

5. Tuberculosis

Remember TB remains a major association worldwide.

Practical diagnostic approach

When a patient presents with erythema nodosum:

1. Confirm the clinical diagnosis.

2. Obtain a detailed drug history.

3. Ask about recent sore throat.

4. Screen for respiratory symptoms.

5. Assess for gastrointestinal symptoms.

6. Consider pregnancy where appropriate.

7. Ask about travel history.

8. Examine for lymphadenopathy and arthritis.

9. Order targeted investigations.

10. Treat the underlying cause.

Useful investigations

Common investigations include:

• Full blood count

• ESR and CRP

• Chest X-ray

• ASO titre

• Throat swab

• TB screening

• Stool investigations when IBD is suspected

• Pregnancy test

• Autoimmune testing if indicated

Practical examples / mini-cases

Mini-case

A 29-year-old woman develops painful red nodules over both shins. She also has ankle pain and a chest X-ray demonstrating bilateral hilar lymphadenopathy.

What is the most likely underlying diagnosis?

A. Tuberculosis

B. Behçet disease

C. Sarcoidosis

D. Crohn's disease

E. Drug-induced erythema nodosum

Answer: C. Sarcoidosis

Explanation

This is the classic presentation of Löfgren syndrome, consisting of:

• Erythema nodosum

• Bilateral hilar lymphadenopathy

• Acute arthritis

This triad is one of the highest-yield associations tested in MRCP Part 1.

Practical study-tip checklist

✔ Learn causes by category rather than memorising isolated diseases.

✔ Always associate erythema nodosum with septal panniculitis without vasculitis.

✔ Remember Löfgren syndrome as a complete triad.

✔ Separate erythema nodosum from pyoderma gangrenosum.

✔ Revise common drug causes before the examination.

✔ Practise mixed-system questions using the Start a mock test and consolidate difficult topics with the MRCP lectures.

Common pitfalls (5 bullets)

• Confusing erythema nodosum with pyoderma gangrenosum.

• Forgetting sarcoidosis as one of the most important causes.

• Missing recent streptococcal infection.

• Assuming skin biopsy is always required despite a classic presentation.

• Forgetting oral contraceptives and sulfonamides as drug triggers.

FAQs

Is erythema nodosum a vasculitis?

No. Histologically, erythema nodosum is a septal panniculitis without vasculitis, making it distinct from cutaneous vasculitic disorders.

What is the commonest infectious cause of erythema nodosum?

Recent Group A streptococcal pharyngitis is one of the commonest infectious associations and is frequently examined in MRCP Part 1.

Which systemic disease is classically associated with erythema nodosum?

Sarcoidosis, particularly Löfgren syndrome, is the classic association. The triad of erythema nodosum, bilateral hilar lymphadenopathy and arthritis should be recognised immediately.

Can medications cause erythema nodosum?

Yes. Common triggers include sulfonamides, penicillins and combined oral contraceptive pills. A careful medication history is essential.

Does erythema nodosum usually scar?

No. Lesions typically resolve over several weeks without ulceration or permanent scarring, although they often leave temporary bruise-like discoloration.

Ready to start?

Mastering pattern recognition is essential for success in MRCP Part 1. Continue your revision with the MRCP Part 1 overview, reinforce knowledge using the Free MRCP MCQs and assess exam readiness with a mock test.

Sources

1. MRCP(UK). https://www.mrcpuk.org

2. British Association of Dermatologists. https://www.bad.org.uk

3. NICE Clinical Knowledge Summaries. https://cks.nice.org.uk

4. Jameson JL, et al. Harrison's Principles of Internal Medicine.

5. Bolognia JL, Schaffer JV, Cerroni L. Dermatology.