Erythema nodosum

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Erythema nodosum is the most common panniculitis. It represents a reactive inflammatory pattern in the septa between fat lobules rather than infection of the skin itself. Tender nodules emerge over days, most often on both shins, and may feel more extensive beneath the skin than their colour suggests. They do not usually suppurate or ulcerate. As inflammation resolves over three to six weeks, lesions change through bruise-like tones and may leave temporary post-inflammatory hyperpigmentation, especially in richly pigmented skin, but not the depressed scarring expected from destructive lobular panniculitis.

The eruption is a signpost to a trigger, not an automatic diagnosis of sarcoidosis. Ask about recent sore throat, cough, tuberculosis contact or travel, diarrhoea or blood, abdominal pain, joint symptoms, pregnancy possibility, new medicines and systemic constitutional change. Examine throat, cervical nodes, chest, abdomen, joints and lower-limb circulation. The yield of testing is highest when guided by local epidemiology and this history: throat sampling and antistreptolysin titres answer different time points, while tuberculosis tests require exposure and imaging context.

Treatment follows severity and cause. A streptococcal infection, active tuberculosis or inflammatory bowel disease receives its own evidence-based therapy; erythema nodosum does not justify empirical antibiotics without infection evidence. Most skin pain improves with reduced weight-bearing, elevation and analgesia. Oral corticosteroid can mask infection and is rarely needed; it belongs to specialist care only after infection and malignancy have been addressed. Failure to improve should trigger a fresh diagnosis rather than a longer sequence of symptomatic prescriptions.

Key points

Erythema nodosum causes crops of hot tender subcutaneous nodules, classically symmetrical over anterior shins, with poorly defined edges and no ulceration.
Lesions evolve like bruises over several weeks from red or violaceous to brown, green-yellow or hyperpigmented and heal without atrophic scar.
In brown or black skin, warmth, deep tenderness and swelling may identify active nodules more reliably than erythema; record residual pigment separately from pain and inflammation.
Fever, malaise and bilateral ankle pain or periarticular swelling can precede or accompany the skin eruption.
Common associations include recent streptococcal infection, sarcoidosis, tuberculosis, inflammatory bowel disease, pregnancy and selected medicines; many cases remain unexplained.
Bilateral hilar lymphadenopathy with erythema nodosum and ankle periarthritis forms Löfgren syndrome, an acute sarcoid phenotype with a generally favourable course.
First-line assessment is a focused history and examination plus FBC, inflammatory markers, throat and infection evaluation and chest imaging when the cause is not already secure.
Biopsy is not required for a classic self-limited presentation; an atypical distribution, ulcer, persistent single nodule or diagnostic uncertainty needs a deep incisional sample containing subcutaneous fat.
First-line treatment addresses the driver and uses rest, leg elevation, cool compresses and simple analgesia; an NSAID is appropriate only when renal, gastrointestinal, cardiovascular, pregnancy and IBD risk permits.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Infectious immune triggers

Recent group-A streptococcal infection is common, while tuberculosis and diverse bacterial, viral or fungal infections matter according to exposure and geography.

Granulomatous and bowel disease

Sarcoidosis and inflammatory bowel disease generate systemic inflammation that can manifest as reactive septal panniculitis, sometimes before the underlying disorder is recognised.

Pregnancy and medicines

Hormonal immune change during pregnancy and selected medicines, including some contraceptives and antimicrobials, can precede a characteristic otherwise unexplained episode.

Idiopathic or malignant association

No driver is found in many self-limited cases, while persistent constitutional or atypical disease occasionally signals lymphoma, leukaemia or another malignancy.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Delayed immune reaction
Antigenic stimulation produces a cell-mediated inflammatory response within subcutaneous tissue rather than direct microbial invasion of each nodule.
2
Fat septa become inflamed
Oedema and mixed inflammatory cells widen connective-tissue partitions between adipose lobules, creating deep tenderness and poorly defined palpable swelling.
3
Miescher granulomas may form
Small radial histiocytic aggregates around clefts can appear within septa and support the pattern, although they are not independently diagnostic.
4
Resolution preserves architecture
Because classic disease is mainly septal and lacks destructive vasculitis, nodules flatten without suppuration, fat necrosis or depressed permanent scarring.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Tender shin nodules

Deep ill-defined painful lumps arise symmetrically over anterior lower legs, with overlying warmth and colour change but no central fluctuation.

Bruise-like evolution

Active red, violaceous or brown nodules flatten through green-yellow or darker pigment over weeks and resolve without ulcer or depressed scar.

Ankle periarthritis

Bilateral ankle pain and oedematous periarticular swelling commonly accompanies the eruption and may impair walking despite preserved joint architecture.

Löfgren constellation

Acute erythema nodosum, ankle periarthritis and bilateral hilar lymphadenopathy strongly supports a characteristic sarcoidosis presentation.

Atypical destructive noduleRed flag

Ulceration, drainage, marked asymmetry, livedoid change, cold tissue or a persistent solitary mass argues against ordinary erythema nodosum.

Systemic driver clues

Sore throat, cough, night sweats, bowel bleeding, weight loss, pregnancy or a new medicine redirects investigation towards a specific trigger.

Red flags requiring action

Unilateral rapid progression, marked systemic toxicity, fluctuance, necrosis, ulceration, calf swelling, absent pulses, severe breathlessness, immunosuppression, persistent fever, weight loss or nodules lasting beyond the expected course requires expedited alternative-diagnosis assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Focused exposure and medicine historyFirst step
Why
Prioritise the likely driver before ordering a broad low-yield panel.
Interpretation and limitations
Time streptococcal illness, respiratory and gastrointestinal symptoms, TB exposure, travel, pregnancy and every new medicine against onset; association still requires clinical plausibility.
02
FBC, CRP or ESR and organ profile
Why
Measure inflammatory burden and identify infection, cytopenia, hepatic disease or a safe treatment baseline.
Interpretation and limitations
Inflammatory markers often rise but are nonspecific; anaemia, abnormal liver tests or persistent leucocytosis may redirect investigation beyond a simple reactive episode.
03
Streptococcal assessment
Why
Find a recent or ongoing throat trigger when history or examination supports it.
Interpretation and limitations
Throat culture or rapid testing detects current infection, whereas rising or raised antistreptolysin and anti-DNase B titres support a preceding immune stimulus and do not prove active bacterial carriage.
04
Chest radiograph
Why
Evaluate sarcoidosis, tuberculosis and other intrathoracic disease in an unexplained or respiratory-associated presentation.
Interpretation and limitations
Bilateral hilar adenopathy supports sarcoidosis but infection and lymphoma remain context-dependent alternatives; a normal film does not exclude extrapulmonary or early disease.
05
Tuberculosis tests
Why
Investigate exposure, epidemiological risk, symptoms or compatible imaging before immunosuppressive treatment.
Interpretation and limitations
IGRA or tuberculin testing indicates sensitisation, not necessarily active disease; symptoms, chest imaging and microbiological sampling determine active pulmonary or extrapulmonary TB.
06
Pregnancy and bowel assessment
Why
Identify common contexts that change investigation and medicine safety.
Interpretation and limitations
Test pregnancy with consent when relevant and use symptoms, FBC, CRP and faecal or endoscopic pathways for suspected IBD rather than attributing diarrhoea to the skin reaction.
07
Deep incisional biopsy
Why
Confirm panniculitis and exclude lobular, vasculitic, infectious or malignant disease when morphology is atypical.
Interpretation and limitations
The sample must include generous subcutaneous fat; classic erythema nodosum shows predominantly septal panniculitis without primary vasculitis, while superficial punch tissue may be nondiagnostic.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Cellulitis or deep infection

Unilateral expanding heat, portal of entry, fluctuance, toxicity or gas suggests bacterial infection rather than symmetrical sterile nodules.

Nodular vasculitis

Posterior calf nodules that ulcerate, with lobular granulomatous inflammation and vasculitis, favour erythema induratum or a related process.

Superficial thrombophlebitis or DVT

A tender venous cord or unilateral calf swelling and thrombosis risk requires vascular examination and ultrasound rather than panniculitis treatment.

Pancreatic or alpha-one panniculitis

Oily draining necrotic nodules with pancreatic disease or ulcerative panniculitis with protease-inhibitor deficiency indicates lobular fat destruction.

Subcutaneous malignancy

Persistent firm asymmetric nodules with constitutional decline or cytopenia can represent lymphoma or leukaemic infiltration and require deep biopsy.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First diagnostic sequenceConfirm the nodule behaves like erythema nodosumFirst stepTender lower-leg nodules appear over days with or without ankle symptoms.

1Palpate depth and borders, compare both legs and document heat, tenderness, colour, ulceration, fluctuance, pulses and calf asymmetry using photographs with consent.
2Ask about throat, chest, TB, bowel, pregnancy, medicine and constitutional clues and examine joints, nodes, chest and abdomen.
3Request FBC, inflammatory markers and chest radiography when unexplained, adding targeted throat, TB, pregnancy or bowel tests rather than a universal autoimmune screen.

02First-line symptom careUnload painful inflamed septaFirst lineThe presentation is typical, circulation is intact and no urgent mimic is present.

1Reduce prolonged standing and impact exercise temporarily, elevate legs and use cool wet compresses while maintaining gentle movement as pain permits.
2Offer paracetamol or a short ibuprofen course only after checking renal, ulcer, bleeding, cardiovascular, asthma, IBD and pregnancy risk.
3Explain the expected bruise-like evolution and review within weeks, with earlier return for ulceration, unilateral spread, respiratory decline or systemic deterioration.

03Cause-directed managementTreat evidence rather than associationTesting identifies streptococcal infection, tuberculosis, sarcoidosis, IBD, pregnancy or a plausible medicine trigger.

1Treat confirmed active infection through its disease-specific antimicrobial pathway and notify tuberculosis as required; do not give antibiotics for an isolated raised titre.
2Coordinate sarcoid or IBD control with respiratory or gastroenterology teams and balance fetal and maternal risk with obstetric input during pregnancy.
3Stop or substitute a suspected medicine with the prescriber when benefit-risk supports it and document the reaction specifically rather than labelling an unrelated class.

04Atypical or persistent routeSample deep and reopen the differentialNodules ulcerate, drain, recur unusually, remain solitary or fail to settle over six to eight weeks.

1Reassess infection, thrombosis, vasculitis, pancreatic disease, alpha-1-antitrypsin disease and subcutaneous malignancy from the changed morphology and systemic picture.
2Arrange a deep incisional biopsy including fat, with portions for culture when infection is possible and prior treatment and lesion age recorded for pathology.
3Seek dermatology and relevant specialty input before systemic corticosteroid, because temporary suppression can obscure infection, lymphoma or another panniculitis.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Reduces pain and ankle inflammation during a typical self-limited episode when supportive measures and paracetamol are insufficient.

Ibuprofen for short-term pain

Take 400 mg by mouth with or after food up to three times daily for the shortest necessary period, leaving at least four hours between doses and not exceeding 1200 mg daily without prescription.

Avoid active peptic ulcer or bleeding, significant renal disease, NSAID-sensitive asthma and the final trimester of pregnancy; review cardiovascular, anticoagulant and interacting-drug risk and avoid during active IBD when it may worsen bowel disease.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Pain and immobility

Deep shin tenderness and ankle periarthritis can limit walking, sleep, work and exercise for several weeks despite a favourable skin outcome.

Residual dyspigmentation

Bruise-like brown or darker marks may remain after inflammation, particularly in richly pigmented skin, and cause distress despite eventual fading.

Missed underlying disease

Failure to investigate a coherent trigger can delay treatment of tuberculosis, sarcoidosis, inflammatory bowel disease, infection or haematological malignancy.

Treatment harm

Unnecessary antibiotics promote adverse effects and resistance, while NSAIDs or premature corticosteroids can worsen renal, gastrointestinal, pregnancy, IBD or infectious risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record the number of new nodules, tenderness, ability to walk, ankle swelling and systemic symptoms rather than judging activity from lingering pigment alone.
Review the result and ownership of chest imaging, throat, TB, bowel and pregnancy investigations and act on incidental lymphadenopathy or cytopenia.
A typical episode should stop generating new lesions and resolve over several weeks; persistence beyond six to eight weeks warrants diagnostic review.
Monitor renal, gastrointestinal, respiratory and bleeding adverse effects during NSAID use and stop promptly when benefit is absent or harm appears.
For identified sarcoid, TB or IBD, follow organ response through that specialty pathway while documenting whether skin and ankle features track activity.
Address temporary mobility, work, sleep and post-inflammatory pigment concerns and provide urgent return advice for ulceration, breathlessness or unilateral vascular symptoms.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Panniculitis lives deep

The palpable lesion often extends beyond visible colour because inflammation lies within subcutaneous septa rather than the superficial epidermis or dermis.

Colour outlasts inflammation

Brown or bruise-like remnants can persist after tenderness and heat resolve, particularly in darker skin, and should not automatically trigger systemic treatment.

Ankles can dominate

Periarticular oedema may cause more functional limitation than the nodules and is a useful clue to the acute sarcoid Löfgren phenotype.

ASO looks backwards

An antistreptolysin response supports recent streptococcal exposure but cannot establish that viable throat bacteria remain or require antibiotics today.

No ulcer is reassuring

Classic erythema nodosum preserves the surface; breakdown or drainage should prompt deep infection, vasculitis, pancreatic panniculitis or another diagnosis.

A punch may be too shallow

When tissue is necessary, an incisional sample with ample fat answers the septal-versus-lobular question better than a superficial routine punch.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every tender red lower-leg lesion cellulitis and prescribing repeated antibiotics for a symmetrical non-infectious eruption.
02
Equating erythema nodosum with sarcoidosis without asking about streptococcus, TB, IBD, pregnancy and medicines.
03
Treating an isolated ASO titre as evidence of current infection requiring antibiotics.
04
Using NSAIDs despite active bowel inflammation, renal injury, ulcer bleeding, anticoagulation or pregnancy risk.
05
Taking a superficial punch that misses subcutaneous fat in an atypical persistent nodule.
06
Starting systemic corticosteroid before infection and malignancy have been adequately considered.
07
Escalating treatment for residual hyperpigmentation after heat and tenderness have resolved.