Extraintestinal manifestations (EIMs) of inflammatory bowel disease

1. Musculoskeletal

• Peripheral arthritis / arthropathy
  • Type 1: acute, asymmetric oligoarthritis, usually large lower-limb joints, associated with active bowel disease
  • Type 2: chronic polyarthritis, often independent of bowel activity
• Arthralgia
• Axial spondyloarthritis
  • Sacroiliitis
  • Ankylosing spondylitis
  • Inflammatory back pain
• Enthesitis
• Dactylitis
• Osteopenia and osteoporosis
• Vertebral compression fractures
• Hypertrophic osteoarthropathy
  • Digital clubbing
  • Periostitis
• Avascular necrosis / osteonecrosis, particularly with corticosteroid exposure
• Rare: periostitis, polymyositis, granulomatous vasculitis, secondary amyloidosis

2. Cutaneous and mucocutaneous

• Erythema nodosum: tender red subcutaneous nodules, classically on the shins; usually parallels IBD activity
• Pyoderma gangrenosum: painful rapidly progressive ulcer with undermined violaceous edges; may be independent of bowel activity
• Aphthous stomatitis / recurrent oral ulcers
• Oral granulomatous Crohn disease, including lip swelling and cobblestoning
• Sweet syndrome: acute febrile neutrophilic dermatosis
• Leukocytoclastic vasculitis / palpable purpura
• Psoriasis
• Hidradenitis suppurativa
• Erythema multiforme
• Acrodermatitis enteropathica due to zinc deficiency
• Skin changes due to nutritional deficiency:
  • Purpura
  • Glossitis
  • Angular cheilitis
  • Alopecia / hair loss
  • Brittle nails
• Perianal skin tags, fissures, fistulae and abscesses in Crohn disease are disease manifestations rather than classic immune EIMs

3. Ocular

• Episcleritis: often parallels bowel activity
• Scleritis
• Anterior uveitis / iritis: painful red eye, photophobia and blurred vision; may occur independently of bowel activity
• Keratitis / corneal ulceration
• Conjunctivitis
• Retinal vasculitis and other retinal vascular disease
• Orbital inflammatory disease, rarely

4. Hepatobiliary and pancreatic

• Primary sclerosing cholangitis (PSC), particularly associated with UC
• Autoimmune hepatitis
• PSC-autoimmune hepatitis overlap syndrome
• Small-duct sclerosing cholangitis
• Pericholangitis
• Portal fibrosis and cirrhosis
• Cholangiocarcinoma risk in PSC
• Fatty liver / metabolic dysfunction-associated steatotic liver disease
• Cholelithiasis, especially with ileal Crohn disease or ileal resection
• Hepatic granulomas
• Portal-vein thrombosis, rarely
• Acute or chronic pancreatitis, including autoimmune pancreatitis and drug-related pancreatitis

5. Renal and genitourinary

• Nephrolithiasis, especially calcium oxalate stones from enteric hyperoxaluria in ileal Crohn disease
• Uric acid stones
• Tubulointerstitial nephritis
• IgA nephropathy and other glomerulonephritides
• Secondary renal amyloidosis
• Fistula-related urinary complications in Crohn disease:
  • Enterovesical fistula
  • Recurrent urinary tract infections
  • Pneumaturia or fecaluria

6. Respiratory

• Bronchiectasis
• Chronic bronchitis / tracheobronchitis
• Small-airway disease, including bronchiolitis
• Organizing pneumonia
• Interstitial lung disease
• Pulmonary nodules or granulomatous lung disease
• Serositis, including pleuritis
• Drug-induced lung toxicity, such as from mesalazine, methotrexate, or anti-TNF treatment

7. Hematologic and vascular

• Iron-deficiency anemia from blood loss
• Anemia of chronic inflammation
• Vitamin B12 or folate deficiency anemia
• Thrombocytosis during active inflammation
• Venous thromboembolism
  • Deep-vein thrombosis
  • Pulmonary embolism
  • Cerebral venous thrombosis
  • Portal or mesenteric venous thrombosis
• Arterial thromboembolism, less commonly

8. Metabolic, nutritional and endocrine

• Growth failure and delayed puberty in children/adolescents
• Delayed sexual maturation
• Malnutrition and sarcopenia
• Vitamin and mineral deficiencies:
  • Iron
  • Vitamin B12
  • Folate
  • Vitamin D
  • Calcium
  • Zinc
  • Magnesium
• Dehydration and electrolyte disturbances
• Secondary amyloidosis
• Associated immune-mediated conditions, such as autoimmune thyroid disease, occur more often but are not always classified as direct EIMs.

High-yield activity relationship

1. General physical examination
2. Abdominal examination for IBD
3. Complete systemic examination
4. Specific system: cardiovascular, respiratory, neurological, etc.

OSCE Physical Examination Checklist: IBD Extraintestinal Manifestations

1. Introduction and preparation

• Wash hands.
• Introduce yourself and confirm patient identity.
• Explain: “I would like to examine you for signs of inflammatory bowel disease outside the bowel, particularly affecting the joints, skin, eyes and liver.”
• Obtain consent.
• Ask about pain, especially in the eyes, joints, back, or skin lesions.
• Ensure adequate exposure: hands, arms, face, oral cavity, legs, abdomen, and lower back as appropriate.
• Position patient sitting initially, then standing and lying supine if needed.
• Offer a chaperone for examination of perianal or genital areas.

2. General inspection

• Ill appearance, pallor, weight loss, cachexia, dehydration.
• Fever or features of active systemic inflammation.
• Walking aids, altered gait, or difficulty mobilising due to arthritis or spinal disease.
• Steroid-related features:
  • Cushingoid appearance
  • Bruising
  • Proximal muscle wasting
• Previous surgical scars, stoma, fistula drainage bags or dressings.

3. Hands and upper limbs

Hands

• Digital clubbing, which may accompany IBD-associated arthropathy or hepatobiliary disease.
• Peripheral cyanosis.
• Palmar erythema, a possible sign of chronic liver disease.
• Leukocytoclastic vasculitis: palpable purpura or non-blanching rash.
• Psoriatic plaques, nail pitting, onycholysis.
• Signs of nutritional deficiency:
  • Koilonychia, brittle nails, pallor suggesting iron deficiency
  • Dry skin or hyperpigmentation

Peripheral joint examination

• Swelling, erythema, warmth, effusion or tenderness in:
  • Wrists
  • MCP and PIP joints
  • Elbows
  • Shoulders, if symptomatic
• Asymmetrical peripheral arthritis, often affecting larger joints and lower limbs.
• Enthesitis: tenderness at tendon insertions, especially:
  • Achilles insertion
  • Plantar fascia insertion
  • Elbow epicondyles
• Dactylitis: diffuse swelling of an entire finger or toe.

4. Face, eyes and mouth

Eyes

• Conjunctival injection.
• Episcleritis: sectoral redness with mild discomfort, often related to bowel activity.
• Anterior uveitis / iritis: circumcorneal redness, photophobia, reduced vision, irregular pupil.
• Scleritis: deep violaceous-red eye with severe pain.
• Reduced visual acuity, if equipment is available.

Mouth

• Aphthous ulcers
• Angular cheilitis
• Glossitis
• Oral candidiasis, particularly in immunosuppressed patients
• Oral Crohn disease:
  • Lip swelling
  • Cobblestoning of oral mucosa
  • Mucosal tags or granulomatous lesions

5. Skin examination

Key IBD skin manifestations

• Erythema nodosum
  • Tender, erythematous subcutaneous nodules
  • Usually over the anterior shins
  • Commonly parallels active intestinal disease
• Pyoderma gangrenosum
  • Painful ulceration with purulent base and undermined violaceous edge
  • Often occurs on the legs or around stomas
  • Do not unnecessarily traumatise lesions because of pathergy
• Sweet syndrome
  • Tender erythematous papules, nodules or plaques, often with fever
• Psoriasis or hidradenitis suppurativa.
• Vasculitic rash or palpable purpura.
• Surgical scars and stoma site:
  • Look for peristomal pyoderma gangrenosum
  • Inspect for fistulae or skin irritation

Lower limbs

• Inspect shins for erythema nodosum and pyoderma gangrenosum.
• Inspect ankles, knees and feet for joint swelling.
• Check Achilles tendons and plantar fascia insertions for enthesitis.

6. Spine and sacroiliac joints

Inspection

• Loss of lumbar lordosis.
• Thoracic kyphosis.
• Reduced spinal movement.
• Asymmetry or scoliosis.

Palpation and movement

• Palpate sacroiliac joints for tenderness.
• Assess lumbar flexion using the modified Schober test, if required.
• Assess lumbar extension and lateral flexion.
• Assess chest expansion in suspected ankylosing spondylitis.
• Perform sacroiliac stress manoeuvres only if appropriate and not excessively painful.

• Sacroiliitis
• Axial spondyloarthritis / ankylosing spondylitis
• Inflammatory back disease features: restricted movement rather than acute focal tenderness.

7. Abdominal examination and hepatobiliary signs

Inspect

• Abdominal distension.
• Scars, stoma, fistulae.
• Visible masses or dilated veins.
• Bruising or skin changes of chronic liver disease.

Palpate

• Hepatomegaly.
• Splenomegaly.
• Right upper-quadrant tenderness.
• Abdominal mass or tenderness.

Look for chronic liver disease

• Jaundice.
• Scratch marks from cholestatic pruritus.
• Spider naevi.
• Palmar erythema.
• Hepatomegaly or splenomegaly.
• Ascites, if suspected.

8. Bone, nutrition and treatment-related complications

• Assess height, posture and thoracic kyphosis where feasible.
• Ask about vertebral pain or fragility fractures.
• Look for features of osteoporosis or vertebral compression fracture.
• Assess muscle bulk for sarcopenia and steroid myopathy.
• Consider proximal muscle power testing if weakness is reported.
• Look for nutritional deficiencies:
  • Pallor
  • Glossitis
  • Angular cheilitis
  • Muscle wasting
  • Dry skin, hair loss or brittle nails

9. Examination not routinely completed in a brief station

“To complete the examination, I would perform a focused neurological assessment for peripheral neuropathy, assess for renal complications such as renal stones or interstitial nephritis, and examine the perianal area with consent and a chaperone for Crohn-related fistulae, fissures, abscesses and skin tags.”

• Respiratory examination if cough, breathlessness or suspected IBD-associated airway/interstitial lung disease.
• Peripheral vascular examination if symptoms suggest venous thromboembolism.
• Genital examination with consent if metastatic Crohn disease or vulval/perineal disease is suspected.

10. Completion

• Thank the patient.
• Help them dress and ensure comfort.
• Wash hands.
• Summarise findings.
• State further assessment.

OSCE summary statement

“I examined this patient for extraintestinal manifestations of inflammatory bowel disease. I looked for peripheral and axial arthropathy, enthesitis, skin lesions such as erythema nodosum and pyoderma gangrenosum, oral aphthae, ocular inflammation including episcleritis and uveitis, signs of hepatobiliary disease including PSC, and consequences of chronic inflammation, malnutrition or corticosteroid therapy such as osteoporosis. I would complete the assessment with vital signs, urinalysis, ophthalmology review if there are ocular symptoms, blood tests including FBC, CRP, liver profile and nutritional markers, and targeted imaging or specialist referral as indicated.”

High-yield EIMs to never miss

1. Peripheral arthritis
2. Sacroiliitis / ankylosing spondylitis
3. Erythema nodosum
4. Pyoderma gangrenosum
5. Aphthous oral ulcers
6. Episcleritis and anterior uveitis
7. Primary sclerosing cholangitis
8. Osteopenia / osteoporosis
9. Venous thromboembolism risk
10. Renal stones, especially with ileal Crohn disease