Department of Medicine

ERYTHEMA NODOSUM
LEARNING OUTCOMES

Define erythema nodosum

List the causes of erythema nodosum
Identify the signs and symptoms of erythema nodosum
Formulate a differential diagnosis for erythema nodosum
Choose appropriate investigations in patients presenting
with erythema nodosum
Outline the management of erythema nodosum
List the complications of erythema nodosum
DEFINITION

Erythema nodosum (EN) is the most common form of

panniculitis (infiltration of subcutaneous tissue by
inflammatory cells).
EN is characterized by erythematous, tender nodules,
typically over the pretibial areas bilaterally.
It is regarded as a delayed hypersensitivity response to
some antigen challenge and is typically an acute process.
EN occurs in a variety of disorders for which the aetiology
remains unknown; for example, sarcoidosis, inflammatory
bowel disease, and Behets disease.
EPIDEMIOLOGY

The annual incidence of erythema nodosum (EN) is

approximately 1 to 5/100,000 persons, most often
women aged 15 to 40 years.
PATHOLOGY

The histopathology of EN shows a neutrophilic

perivascular reaction with septal panniculitis in the deep
dermis and subcutaneous tissue, with the epidermis
appearing normal.
RISK FACTORS
Recent Streptococcal infection (e.g. streptococcal pharyngitis)
Other infections (viral URTIs, gastroenteritis, atypical pneumonias) etc
Drugs (sulphonamides, oral contraceptives)
Sarcoidosis
Tuberculosis
Inflammatory bowel disease (Crohns disease)
Deep fungal infections (e.g. coccidioidomycosis and blastomycosis)
Lymphoma
Behets disease
SYMPTOMS

Polyarthralgia, fever, and malaise frequently accompany

erythema nodosum (EN) (sometimes in advance of skin
findings)

Red or violet tender nodules occur in crops on the shins

and, less commonly, on the forearms, thighs or trunk.
 SIGNS
EN is characterised by the presence of rounded or oval, slightly raised,
non-ulcerative painful red nodules in the subcutaneous fatty tissue.
Nodules tend to be:
Symmetrical in distribution, 1 to 6 cm in diameter, sometimes
coalescing
Usually located bilaterally on the lower extremities, on the anterior
tibial surface, (they may also involve the ankles, the lower parts of
the thighs, and the forearms).
Nodules are self limiting, resolving in one to six weeks.
They evolve from bright red to a brownish yellow discoloration
resembling bruises.
Old lesions often coexist with the appearance of new nodules, so
that nodules at various stages of their evolution may be observed.
Erythema nodosum
Erythema nodosum
DIFFERENTIAL DIAGNOSIS

Nodular vasculitis (erythema induratum)

Subcutaneous infections due to bacteria or fungi
Superficial thrombophlebitis
Cutaneous vasculitis
INVESTIGATIONS Underlying aetiology
The diagnosis of EN is most often clinical, with biopsy required only in
atypical cases.
The following diagnostic testing is recommended to help establish a
probable cause or the presence of an associated disease:
A throat swab
Antistreptolysin-O titre
Chest X-ray to assess for hilar lymphadenopathy or other evidence
of pulmonary sarcoidosis, tuberculosis, or fungal infection
Tuberculin skin test (Mantoux test), Quantiferon test to rule out TB
Complete blood count and differential to screen for infections
Liver enzyme (aminotransferases, alkaline phosphatase), bilirubin,
albumin (baseline before starting treatment for the underlying
condition)
Serum creatinine and urea nitrogen (baseline before starting
treatment e.g. NSAIDs)
 MANAGEMENT- Symptomatic

EN is usually self-limited or resolves with treatment of the

underlying disorder.
Treatment is typically symptomatic (including nonsteroidal
anti-inflammatory drugs (NSAIDs).
Treatment with antibiotics is generally not warranted in
patients with EN thought related to streptococcal infection, if
such suspicion is based solely upon serological evidence of
recent streptococcal infection or a positive throat culture in
the absence of symptomatic pharyngitis.
Glucocorticoids are usually not necessary for idiopathic EN.
COMPLICATIONS

Serious complications are unusual unless part of the

underlying disease

Chronic or recurrent disease is rare

Lesions heal without atrophy or scarring

PROGNOSIS

The course of erythema nodosum depends on the

underlying cause of the illness.
Individual nodules remain for about 2 weeks, but new
nodules may form for 3 to 4 weeks after the first eruption.
Spontaneous resolution of the condition usually within 6 to
8 weeks.
May be more protracted,
If the underlying cause remains
Idiopathic EN
References
1. R. Marks, R. Motley: Common Skin Diseases.,18th edition, 2011
2. J. Manaa, J. Marcoval: Erythema nodosum., Clinics in Dermatology
(2007) 25, 288294
3. Gonzlez-Gay MA, Garca-Porra C, Pujol RM, Salvarani C.
Erythema nodosum: a clinical approach. Clin Exp Rheumatol 2001;
19:365.
4. J.E. Fitzpatrick, J.G. Morelli: Dermatology Secrets in colour., 3rd
edition, 2007
5. R.G. Brown, T. Burns: Dermatology lecture notes., 9th edition 2007
6. UpToDate: Erythema nodosum
7. DermnetNZ: Erythema nodosum
MCQ 1
A 34 year old female is reviewed in the Dermatology
outpatient clinic. She has tender, raised red nodules on her
shins and is felt to have erythema nodosum. Which of the
following is the most likely underlying cause?

A. Recent streptococcal infection

B. TB infection
C. Yersinia infection
D. Inflammatory bowel disease
E. Sarcoidosis

Answer: A
(Slide 6)
MCQ 2
A 32 year old man presented with tender erythematous
nodules on his shin. The clinical impression was erythema
nodosum. A skin biopsy was performed to confirm the
diagnosis. What is the finding in the histopathological
examination of the skin biopsy specimen which fits the
diagnosis?

A. Acantholysis
B. Panniculitis
C. Hyperkeratosis
D. Vasculitis
E. Spongiosis

Answer: B
(Slide 5)
MCQ 3
A 24 year old female has returned from holidays in Malaysia.
Four weeks later she presented to GP with profuse night
sweating, weight loss, cough and painful red nodules on her
lower limbs. What is the most likely cause for her clinical
presentation?
A. Deep fungal infection
B. Behcets disease
C. Tuberculosis
D. Idiopathic
E. Inflammatory bowel disease

Answer: C
(Slide 6)
 MEQ
A 19 year old female presents to her GP with a 1 week history
of a severe sore throat. She is able to drink fluids but
complains of pain on swallowing. She has exudate on both
tonsils & cervical lymphadenopathy. She also has tender, red
nodules on both shins for the past 1 day that are very
uncomfortable.

Q1. What is the most likely diagnosis for the skin disorder? (2 marks)
Erythema nodosum

Q2. What is the most likely underlying cause? (2 marks)

Streptococcal throat infection
 MEQ
Q3. List 4 differential diagnosis for the skin lesions. (8 marks)
Nodular vasculitis (erythema induratum)
Subcutaneous infections due to bacteria or fungi
Superficial thrombophlebitis
Cutaneous vasculitis
Q4. List 4 investigations to investigate the possible underlying
causes & give a reason for each. (8 marks)
ASO titres (anti-streptolysin antibodies) strep infection
Throat swab strep infection
Chest X-ray to assess for sarcoidosis, TB
Tuberculin skin test (Mantoux test) / Quantiferon test for TB