What is the best next step in managing a patient presenting with a mild tender rash on the shins, joint pain, and bilateral hilar enlargement on chest radiograph, with consideration of determining Angiotensin-Converting Enzyme (ACE) level or biopsy of the rash to evaluate for non-caseating granulomas?

Management of Suspected Sarcoidosis with Erythema Nodosum and Bilateral Hilar Adenopathy

The best next step in managing this patient with tender shin rash, joint pain, and bilateral hilar adenopathy is to determine the angiotensin-converting enzyme (ACE) level as part of the diagnostic workup for sarcoidosis.

Clinical Presentation Analysis

The patient's presentation strongly suggests Löfgren's syndrome, a specific presentation of sarcoidosis characterized by:

• Bilateral hilar adenopathy on chest radiograph
• Erythema nodosum (tender rash on shins)
• Periarticular arthritis (joint pain)

This constellation of findings is classified by the American Thoracic Society as "highly probable" for sarcoidosis 1, 2.

Diagnostic Approach

Laboratory Testing

• ACE level determination: While not perfectly sensitive or specific, elevated serum ACE (>50% of upper limit of normal) is considered a supportive finding for sarcoidosis 1, 2
• ACE is synthesized by sarcoid granulomas, making it a useful diagnostic marker 3
• Additional recommended laboratory tests include:
  • Serum calcium and vitamin D levels
  • Liver function tests
  • Complete blood count
  • Renal function tests

Biopsy Considerations

• Biopsy of the rash to evaluate for non-caseating granulomas would be appropriate if:
  • The clinical presentation is atypical for Löfgren's syndrome
  • Initial laboratory tests are inconclusive
  • There is suspicion for alternative diagnoses

Rationale for ACE Level as Next Step

1. The patient presents with a highly characteristic clinical picture of Löfgren's syndrome
2. ACE level is a non-invasive test that can provide supportive evidence for sarcoidosis
3. The American Thoracic Society guidelines list ACE level as a "probable" supportive test for sarcoidosis diagnosis 1

Clinical Decision Algorithm

1. Patient with tender shin rash + joint pain + bilateral hilar adenopathy
2. First step: Determine ACE level and other laboratory tests
   • If ACE elevated: Supports sarcoidosis diagnosis
   • If ACE normal: Does not rule out sarcoidosis (sensitivity limitations)
3. Consider biopsy if:
   • Diagnostic uncertainty persists
   • Atypical features present
   • Need to exclude alternative diagnoses

Important Caveats

• ACE level limitations: While elevated in many sarcoidosis patients, ACE has imperfect sensitivity and specificity 4, 5

  • Only 73% of patients with active sarcoidosis not on corticosteroids have elevated ACE 4
  • ACE is more likely to be elevated in patients with pulmonary parenchymal involvement than those with only hilar adenopathy 4

• Diagnostic criteria: The diagnosis of sarcoidosis requires three elements 2:

  1. Compatible clinical presentation (present in this case)
  2. Histopathologic evidence of non-caseating granulomas (would require biopsy)
  3. Exclusion of alternative causes

• Differential diagnosis: Must consider other granulomatous diseases including:

  • Tuberculosis
  • Fungal infections
  • Lymphoma
  • Berylliosis
  • Vasculitides

Follow-up Considerations

After ACE level determination, management should be guided by:

• Severity of symptoms
• Extent of organ involvement
• Disease progression

Regular follow-up for disease monitoring would be appropriate for patients with Löfgren's syndrome, as this presentation often has a favorable prognosis with spontaneous resolution within 2 years in most cases 1.