Question

A 31-year-old woman attends her family doctor because she has developed several tender, red, raised lumps over the fronts of both lower legs. She also mentions a mild, thin, white vaginal discharge without smell.

During the past few days she has felt more nauseated than usual and has noticed that she is passing urine more often. She has no burning on urination, no visible blood in the urine, no fever, cough, weight loss, or night sweats.

What is the most appropriate next investigation?

A. Excision biopsy of one of the nodules
B. Endocervical NAAT for chlamydia and gonorrhoea
C. Pregnancy test
D. Chest CT to look for hilar lymphadenopathy
E. Urine dipstick and culture only

Answer

C. Pregnancy test

Detailed explanation

This patient has a classic description of erythema nodosum: painful, erythematous, raised nodules, most commonly over the shins. Erythema nodosum is a panniculitis, meaning inflammation of the subcutaneous fat. It is not a specific disease by itself, but a reactive pattern that can be triggered by infections, inflammatory disease, drugs, malignancy, and pregnancy.

The key clue in this question is that the associated symptoms all fit early pregnancy: nausea, urinary frequency, and a thin, white, non-offensive vaginal discharge, which may represent physiological leucorrhoea of pregnancy. Pregnancy is a recognised cause of erythema nodosum.

Therefore, the most appropriate next investigation is a pregnancy test.

In exam questions, when erythema nodosum appears with symptoms suggestive of pregnancy, always consider pregnancy as the unifying diagnosis before chasing rarer causes such as tuberculosis, sarcoidosis, inflammatory bowel disease, or malignancy.

Why the other options are wrong

A. Excision biopsy of one of the nodules
Biopsy is usually unnecessary when the clinical picture is typical of erythema nodosum and there is an obvious likely trigger. Erythema nodosum classically presents as tender nodules on the shins and usually resolves without scarring. A biopsy would be invasive and would not be the best next step here.

B. Endocervical NAAT for chlamydia and gonorrhoea
Chlamydia and gonorrhoea may cause abnormal vaginal discharge, pelvic pain, intermenstrual bleeding, or postcoital bleeding, but they do not neatly explain the nausea, urinary frequency, and erythema nodosum in this case. The discharge described is thin, white, and odourless, which is more consistent with physiological discharge in pregnancy than sexually transmitted infection.

D. Chest CT to look for hilar lymphadenopathy
Sarcoidosis is an important cause of erythema nodosum, especially in Löfgren syndrome, where erythema nodosum may occur with bilateral hilar lymphadenopathy, fever, and arthralgia. However, this patient has no respiratory symptoms, systemic features, or joint symptoms. Also, CT is not the first-line screening test if sarcoidosis or tuberculosis is suspected; a chest X-ray is usually used initially.

E. Urine dipstick and culture only
Urinary frequency can occur in urinary tract infection, but this patient has no dysuria, haematuria, fever, suprapubic pain, or loin pain. UTI also would not explain the erythema nodosum or the physiological-type vaginal discharge. Pregnancy explains all the symptoms better.

Key exam point

Erythema nodosum plus nausea, urinary frequency, and thin white odourless vaginal discharge should make you think of pregnancy; the next investigation is a pregnancy test.

Very important clinical trap

Do not automatically investigate erythema nodosum with biopsy or extensive systemic testing if the stem gives a clear reversible trigger. In young women, pregnancy and the combined oral contraceptive pill are common exam-relevant causes. The diagnosis of erythema nodosum is usually clinical.

Cheat sheet for exam

• Erythema nodosum = tender red nodules, usually on shins.
• Pathology = inflammation of subcutaneous fat, a type of panniculitis.
• Lesions usually resolve within around 6 weeks.
• Healing is usually without ulceration or scarring.
• Common causes: streptococcal infection, tuberculosis, sarcoidosis, inflammatory bowel disease, Behçet disease, drugs, pregnancy, malignancy.
• Drug causes: penicillins, sulphonamides, combined oral contraceptive pill.
• Pregnancy can cause erythema nodosum.
• Physiological pregnancy symptoms: nausea, urinary frequency, breast tenderness, fatigue.
• Physiological vaginal discharge in pregnancy is often thin, white, and non-offensive.
• Fishy discharge suggests bacterial vaginosis.
• Offensive frothy discharge suggests Trichomonas vaginalis.
• Thick curd-like discharge suggests Candida.
• Erythema nodosum with bilateral hilar lymphadenopathy and arthralgia suggests Löfgren syndrome.
• Erythema nodosum with diarrhoea, abdominal pain, or bloody stool suggests inflammatory bowel disease.
• Erythema nodosum with sore throat may suggest streptococcal infection.
• Initial investigations for unclear erythema nodosum may include FBC, CRP/ESR, throat swab, chest X-ray, and targeted tests based on history.
• Biopsy is reserved for atypical lesions or diagnostic uncertainty.
• In a woman of reproductive age with compatible symptoms, pregnancy test is often the simplest and highest-yield next step.

Flash cards

Q: What is erythema nodosum?
A: A panniculitis causing tender, red, raised nodules, classically on the shins.

Q: What layer of tissue is inflamed in erythema nodosum?
A: The subcutaneous fat.

Q: Does erythema nodosum usually scar?
A: No. It usually resolves without ulceration or scarring.

Q: Name four important causes of erythema nodosum.
A: Streptococcal infection, tuberculosis, sarcoidosis, inflammatory bowel disease, drugs, and pregnancy.

Q: Which pregnancy-related symptoms in a question may point towards pregnancy as the cause of erythema nodosum?
A: Nausea, urinary frequency, breast tenderness, missed period, fatigue, and thin white odourless vaginal discharge.

Q: What is the best next investigation in a woman with erythema nodosum and symptoms suggestive of early pregnancy?
A: Pregnancy test.

Q: What discharge is typical of bacterial vaginosis?
A: Thin grey-white discharge with a fishy odour.

Q: What discharge is typical of Candida?
A: Thick, white, curd-like discharge, often with vulval itching.

Q: What triad suggests Löfgren syndrome?
A: Erythema nodosum, bilateral hilar lymphadenopathy, and ankle arthritis or arthralgia.

Q: When should biopsy be considered in suspected erythema nodosum?
A: When the lesions are atypical, ulcerating, persistent, in an unusual site, or the diagnosis is uncertain.

MCQs

1. A 27-year-old woman presents with tender red nodules on both shins. She also has morning nausea, urinary frequency, and a thin white odourless vaginal discharge. What is the best next investigation?

A. Skin biopsy
B. Pregnancy test
C. Chest X-ray
D. High vaginal swab
E. Colonoscopy

Answer: B. Pregnancy test

Explanation: The lesions are typical of erythema nodosum. Nausea, urinary frequency, and physiological-type vaginal discharge point towards pregnancy, which is a recognised cause. Pregnancy test is the most appropriate next investigation.

2. Which of the following is the pathological process in erythema nodosum?

A. Leukocytoclastic vasculitis of dermal capillaries
B. Granulomatous inflammation of hair follicles
C. Inflammation of subcutaneous fat
D. Autoimmune destruction of melanocytes
E. Necrosis of the epidermis

Answer: C. Inflammation of subcutaneous fat

Explanation: Erythema nodosum is a panniculitis, meaning inflammation of subcutaneous adipose tissue. It presents with tender nodules, usually on the anterior shins.

3. Which of the following is false regarding erythema nodosum?

A. It commonly affects the shins
B. It may be caused by pregnancy
C. It usually heals with marked scarring
D. It may be associated with sarcoidosis
E. It may follow streptococcal infection

Answer: C. It usually heals with marked scarring

Explanation: Erythema nodosum usually resolves without ulceration or scarring. Scarring would be atypical and should prompt reconsideration of the diagnosis.

4. A patient has erythema nodosum, bilateral hilar lymphadenopathy, fever, and ankle pain. What is the most likely underlying diagnosis?

A. Sarcoidosis
B. Pregnancy
C. Behçet disease
D. Gonorrhoea
E. Hypothyroidism

Answer: A. Sarcoidosis

Explanation: Erythema nodosum with bilateral hilar lymphadenopathy and ankle arthralgia or arthritis is classic for Löfgren syndrome, an acute presentation of sarcoidosis.

5. Which of the following drugs is a recognised trigger for erythema nodosum?

A. Paracetamol
B. Metformin
C. Omeprazole
D. Combined oral contraceptive pill
E. Salbutamol

Answer: D. Combined oral contraceptive pill

Explanation: Recognised drug causes include the combined oral contraceptive pill, penicillins, and sulphonamides.

6. A woman with tender shin nodules has a thin grey discharge with a fishy smell. Which diagnosis best explains the vaginal discharge?

A. Candida
B. Bacterial vaginosis
C. Physiological pregnancy discharge
D. Genital herpes
E. Lichen sclerosus

Answer: B. Bacterial vaginosis

Explanation: Bacterial vaginosis classically causes a thin grey-white discharge with a fishy odour. Physiological pregnancy discharge is usually white or clear and non-offensive.

7. Which of the following is the best description of typical erythema nodosum lesions?

A. Painless vesicles on an erythematous base
B. Tender erythematous nodules over the shins
C. Silvery plaques on extensor surfaces
D. Target lesions involving palms and soles
E. Burrows in finger webs

Answer: B. Tender erythematous nodules over the shins

Explanation: Erythema nodosum typically causes painful red nodules over the anterior lower legs. Vesicles suggest herpes, silvery plaques suggest psoriasis, target lesions suggest erythema multiforme, and burrows suggest scabies.

8. Which of the following is false regarding common causes of erythema nodosum?

A. Streptococcal infection may trigger it
B. Tuberculosis may trigger it
C. Inflammatory bowel disease may trigger it
D. Pregnancy may trigger it
E. Atopic eczema is the most common systemic association

Answer: E. Atopic eczema is the most common systemic association

Explanation: Atopic eczema is not a classic systemic association of erythema nodosum. Important causes include infection, sarcoidosis, inflammatory bowel disease, Behçet disease, drugs, malignancy, and pregnancy.

9. A 34-year-old woman develops erythema nodosum after a sore throat. Which investigation is most relevant if streptococcal infection is suspected?

A. Throat swab
B. Serum amylase
C. Faecal calprotectin only
D. Serum cortisol
E. D-dimer

Answer: A. Throat swab

Explanation: Streptococcal infection is a common trigger of erythema nodosum. A throat swab or streptococcal serology may be considered depending on timing and clinical context.

10. Which of the following best distinguishes physiological vaginal discharge of pregnancy from infective discharge?

A. It is usually green and frothy
B. It is always associated with fever
C. It is usually thin or milky white and non-offensive
D. It causes severe vulval ulceration
E. It is usually associated with haematuria

Answer: C. It is usually thin or milky white and non-offensive

Explanation: Physiological leucorrhoea in pregnancy is commonly thin, white or milky, and non-offensive. Offensive, itchy, green, frothy, or curd-like discharge suggests infection.

11. A patient with erythema nodosum also has chronic diarrhoea, abdominal pain, and weight loss. Which associated condition should be considered?

A. Parkinson disease
B. Inflammatory bowel disease
C. Nephrotic syndrome
D. Hyperparathyroidism
E. Myasthenia gravis

Answer: B. Inflammatory bowel disease

Explanation: Erythema nodosum is an extra-intestinal manifestation of inflammatory bowel disease, especially Crohn’s disease and ulcerative colitis.

12. Which of the following is false about investigating erythema nodosum?

A. Investigation should be guided by history and examination
B. Chest X-ray may be useful if sarcoidosis or tuberculosis is suspected
C. Pregnancy test is appropriate when pregnancy symptoms are present
D. Biopsy is mandatory in every typical case
E. Inflammatory markers may be raised

Answer: D. Biopsy is mandatory in every typical case

Explanation: Erythema nodosum is often a clinical diagnosis. Biopsy is not mandatory in typical cases and is generally reserved for atypical, persistent, ulcerating, or diagnostically uncertain lesions.

Summary for quick exam revision

Erythema nodosum is a panniculitis, meaning inflammation of the subcutaneous fat, and it classically presents with tender, red, raised nodules over the anterior shins. The lesions usually resolve within about 6 weeks and typically heal without scarring. It is not a single disease but a reaction pattern with many possible triggers. Important causes include streptococcal infection, tuberculosis, sarcoidosis, inflammatory bowel disease, Behçet disease, lymphoma or other malignancy, drugs, and pregnancy. Drug triggers include penicillins, sulphonamides, and the combined oral contraceptive pill. In a woman of reproductive age, pregnancy is an important and easily missed cause. Nausea, urinary frequency, fatigue, breast tenderness, and a thin white odourless vaginal discharge are clues to pregnancy. Therefore, erythema nodosum plus these symptoms should be investigated first with a pregnancy test. Do not rush to biopsy typical erythema nodosum if the history gives a likely trigger. Biopsy is mainly useful when the lesions are atypical, ulcerating, persistent, unusually located, or diagnostically unclear. Sarcoidosis should be suspected when erythema nodosum occurs with bilateral hilar lymphadenopathy and ankle arthralgia, known as Löfgren syndrome. Streptococcal infection should be considered after sore throat, and inflammatory bowel disease should be considered with diarrhoea, abdominal pain, blood in stool, or weight loss. Vaginal discharge clues are useful: fishy discharge suggests bacterial vaginosis, curd-like itchy discharge suggests Candida, and offensive frothy discharge suggests Trichomonas. The central exam trick is to find the one diagnosis that explains all the symptoms together; in this case, pregnancy explains the erythema nodosum, nausea, urinary frequency, and physiological vaginal discharge.