Erythema Nodosum: Symptoms, Types, Causes and Treatment

Erythema nodosum (EN) is much more than just a skin condition—it’s a window into what’s happening inside the body. For many, the first sign is the sudden appearance of tender, red nodules on the legs. But behind these lesions can lie a wide variety of triggers, from infections to medications and even systemic diseases. Understanding the symptoms, types, causes, and treatments of erythema nodosum is crucial for patients and clinicians alike, as this condition often demands looking beyond the skin to uncover the full story.

Symptoms of Erythema Nodosum

Erythema nodosum typically presents with a distinct set of symptoms that are hard to ignore. Though its hallmark is painful, red nodules—usually found on the lower legs—the condition can also include a variety of systemic and joint-related symptoms. Recognizing these signs early can aid in both diagnosis and the search for any underlying disease.

Symptom	Description	Location/Pattern	Source(s)
Nodules	Tender, erythematous, subcutaneous, rounded nodules	Primarily anterior lower legs, often bilateral and symmetrical	2 3 4 5
Pain	Common, often severe; worsens with pressure	At sites of nodules	1 2 5
Color Change	Nodules fade from red to purple to yellowish-green	Over days to weeks	5
Systemic	Fever, malaise, fatigue, arthralgia (joint pain), sometimes joint swelling	Often precedes or accompanies nodules	3 4 5

Table 1: Key Symptoms

Nodules: The Hallmark Feature

The most distinctive feature of erythema nodosum is the sudden onset of tender, red nodules. These nodules are usually:

• Located on the front (anterior) of the lower legs, but can also appear on the thighs, forearms, or trunk in some cases 2 3 4.
• Bilateral and symmetrical in distribution.
• Round or oval, measuring between 1 and 5 centimeters in diameter 4.
• Painful to touch, especially in the early stages 1 2.
• Non-ulcerating, meaning they do not break down or form open sores 2.
• Color changes: Nodules often transition from bright red to bluish, then yellowish-green as they resolve, similar to a bruise 5.

Systemic Symptoms

EN is often accompanied by systemic symptoms that can precede or occur along with the nodules:

• Fever and malaise are common, making patients feel generally unwell 3 4 5.
• Arthralgia (joint pain) and even joint swelling can occur, especially in larger joints like the ankles and knees. In some studies, over half the patients experienced joint pain 5.
• Fatigue is also frequently reported.

Symptom Progression and Duration

• The rash often appears suddenly and may last between 2 and 6 weeks, with individual nodules resolving without scarring 4 9.
• Some patients experience recurrences, but for many, EN is a one-time event 9.

Types of Erythema Nodosum

Erythema nodosum is not a one-size-fits-all diagnosis. It presents in various forms, each with distinguishing features. Recognizing these types helps in understanding the disease course, its underlying causes, and guiding management.

Type	Description	Distinct Features	Source(s)
Classic (Acute) EN	Sudden onset, resolves in weeks	Painful nodules, systemic symptoms; self-limited	4 7
Chronic EN	Persistent or recurring nodules (>6 weeks)	Longer duration, may relapse; less severe pain	1 7
Migratory EN	Moving plaques or nodules	Lesions migrate over time	7
EN Leprosum (ENL)	Complication of leprosy	Severe, multisystem symptoms	1 11

Table 2: Types of Erythema Nodosum

Classic (Acute) Erythema Nodosum

This is the most common form:

• Rapid onset of symptoms, often after a triggering event such as infection.
• Nodules typically resolve in 2–6 weeks.
• Systemic symptoms like fever, malaise, and joint pain are frequent 4.

Chronic Erythema Nodosum

• Nodules persist for more than 6 weeks or recur over months or years 1 7.
• Pain may be less intense than in acute cases.
• Often associated with chronic underlying diseases.

Migratory Erythema Nodosum

• This rare form presents as migrating plaques or nodules, which change location over time.
• Lesions may become confluent and move from one site to another 7.

Erythema Nodosum Leprosum (ENL)

• ENL is a distinct, severe immune-mediated complication seen in borderline lepromatous and lepromatous leprosy 1 11.
• Unlike classic EN, ENL is characterized by multisystem involvement, including skin, nerves, joints, eyes, and other organs.
• Requires specific immunosuppressive treatment and has a more serious prognosis 1 11.

Causes of Erythema Nodosum

EN is not a disease itself but a reaction pattern, often pointing to an underlying cause. Its etiology is diverse, making a thorough investigation essential to identify and treat the root issue.

Cause Category	Examples / Specific Causes	Frequency / Notes	Source(s)
Infections	Streptococcal pharyngitis, tuberculosis, other bacteria, deep fungal infections, viruses	Most common cause in children and adults; up to 50% identified	2 8 9 10 12
Systemic Disease	Sarcoidosis, inflammatory bowel disease, cancer, autoimmune diseases	Sarcoidosis frequent in adults; paraneoplastic in rare cases	2 3 10 12
Drugs	Oral contraceptives, antibiotics, others	Less common; notable in women	2 4 10
Other/Idiopathic	Pregnancy, vaccines, unknown	~35–50% remain idiopathic	4 10

Table 3: Main Causes of Erythema Nodosum

Infections

• Streptococcal infections are the leading cause, especially in children and young adults 2 8 9.
• Tuberculosis is a significant cause in regions where it is endemic 2 9 10 16.
• Other infectious triggers include:
  • Deep fungal infections
  • Viral illnesses
  • Mycobacterium and other bacteria 8 9 12

Systemic Diseases

• Sarcoidosis is a prominent cause in adults, particularly in certain populations 10 12.
• Inflammatory bowel diseases (e.g., Crohn’s disease, ulcerative colitis) are also associated 2 10.
• Malignancies: Erythema nodosum can be a paraneoplastic sign, warranting oncological vigilance in atypical or persistent cases 3 10 12.
• Autoimmune/rheumatic diseases are less common but possible 10.

Medications and Other Triggers

• Drugs: Oral contraceptives and some antibiotics are well-recognized causes, especially in women 2 10.
• Pregnancy and certain vaccines have also been linked 4 10.
• In many cases (35–50%), no cause is found, and these are termed idiopathic 4 10.

Special Case: Erythema Nodosum Leprosum

• ENL is specifically tied to lepromatous leprosy and is not caused by the usual triggers of classic EN 1 11.

Treatment of Erythema Nodosum

Treatment of EN focuses on addressing the underlying cause when possible, alongside symptomatic relief. Most cases are benign and self-limiting, but chronic, severe, or complicated presentations—such as ENL—require more intensive therapy.

Therapy Type	Main Options / Interventions	Indication / Notes	Source(s)
Supportive Care	Bed rest, leg elevation, compression	All patients; first-line	4 6
Pain Relief	NSAIDs (ibuprofen, naproxen), analgesics	For pain and inflammation	2 4 6
Specific Therapy	Treat underlying cause: antibiotics (for infection), antitubercular therapy, discontinue offending drug	Etiology-specific	2 4 6 16
Advanced Therapy	Potassium iodide, colchicine, corticosteroids	Chronic/severe/refractory cases	6 15
ENL-specific	Thalidomide, clofazimine, corticosteroids	Erythema nodosum leprosum only	1 13 14

Table 4: Treatment Approaches

Supportive and Symptomatic Care

• Bed rest and leg elevation help reduce discomfort and swelling 4 6.
• Compression stockings may be used for additional support.
• NSAIDs (nonsteroidal anti-inflammatory drugs) are the mainstay for managing pain and inflammation 2 4 6.
• Most cases resolve within a few weeks without lasting effects or scarring 2 4.

Treating the Underlying Cause

• Infections: Appropriate antibiotics or antifungals should be used; for example, penicillin for streptococcal infection 2 4.
• Tuberculosis: Antitubercular therapy is effective, even in patients without overt TB symptoms but with a positive Mantoux test, especially where TB is common 16.
• Discontinue causative drugs if a medication is identified as the trigger 2 4.

Advanced and Adjunctive Therapies

• Potassium iodide has shown efficacy in speeding up resolution, especially in chronic or recurrent cases 6 15.
• Colchicine and systemic corticosteroids may be considered in severe or resistant cases, but corticosteroids are used cautiously due to potential side effects 6.
• Biopsy is rarely needed unless the diagnosis is unclear or atypical features are present 2 4.

Management of Erythema Nodosum Leprosum (ENL)

• Thalidomide is the treatment of choice for ENL, rapidly resolving skin and systemic symptoms; however, it is strictly regulated due to teratogenicity and side effects 13 14.
• Clofazimine and corticosteroids are alternatives, particularly when thalidomide is contraindicated 1 14.
• ENL often requires long-term immunosuppression and multidisciplinary management due to potential involvement of nerves, eyes, and internal organs 1 11 14.

Monitoring and Prognosis

• Most cases of EN are self-limited and recur rarely 4 9.
• Chronic or recurrent cases warrant further workup for hidden causes, including malignancy or systemic disease 3 10.
• ENL is more severe, with higher risk of morbidity and requires close monitoring for complications of both the disease and its treatment 1 11.

Conclusion

Erythema nodosum is a complex and revealing medical condition—one that often signals deeper processes occurring within the body. Whether it is a reaction to infection, a sign of systemic disease, or a complication of leprosy, understanding EN’s symptoms, types, causes, and treatments enables better patient care and outcomes.

Key Points Covered:

• Symptoms: EN presents with painful, red nodules on the legs and may be accompanied by systemic symptoms like fever, malaise, and joint pain 2 3 4 5.
• Types: It includes acute, chronic, migratory, and EN leprosum, each with unique features and implications 1 4 7 11.
• Causes: Infections (especially streptococcal), systemic diseases (sarcoidosis, IBD, cancer), drugs, pregnancy, and idiopathic forms make EN a diagnostic challenge 2 3 4 8 9 10 12.
• Treatment: Most cases resolve with supportive care and NSAIDs, but addressing the underlying cause is crucial. Advanced therapies include potassium iodide, colchicine, and, for ENL, thalidomide or clofazimine 1 6 13 14 15 16.
• Prognosis: EN is usually self-limiting, but ENL and chronic cases require specialized management and careful follow-up 1 4 11.

By recognizing EN for what it is—both a skin condition and a systemic signal—patients and clinicians can work together to uncover and address the underlying causes, ensuring the best possible care.