What is the diagnosis and treatment for a patient with normocytic anemia, elevated WBC, hypocalcemia, vitamin D deficiency, and hilar lymphadenopathy?

Sarcoidosis: Diagnosis and Treatment for Patient with Normocytic Anemia, Elevated WBC, Hypocalcemia, Vitamin D Deficiency, and Hilar Lymphadenopathy

The constellation of hilar lymphadenopathy, normocytic anemia, elevated WBC, hypocalcemia, and vitamin D deficiency strongly suggests sarcoidosis as the most likely diagnosis, requiring corticosteroid therapy as first-line treatment. 1, 2

Diagnostic Evaluation

Clinical Features Supporting Sarcoidosis

• Hilar lymphadenopathy: Bilateral hilar adenopathy on chest imaging is classified as a "highly probable" diagnostic feature of sarcoidosis 1
• Laboratory abnormalities:
  • Normocytic anemia: Common hematologic manifestation in sarcoidosis
  • Elevated WBC: May indicate inflammatory response
  • Hypocalcemia with vitamin D deficiency: Represents abnormal vitamin D metabolism characteristic of sarcoidosis 1, 3

Recommended Diagnostic Workup

1. Imaging studies:

   • Chest CT scan to better characterize hilar lymphadenopathy and assess for perilymphatic nodules or parenchymal involvement 2
   • Consider PET scan if extrapulmonary involvement is suspected 1

2. Laboratory tests:

   • Complete vitamin D profile (25-OH and 1,25-OH vitamin D levels)
   • Serum ACE level (elevated in approximately 60% of sarcoidosis patients) 2
   • Serum calcium and 24-hour urinary calcium
   • Liver function tests (alkaline phosphatase often elevated) 1
   • Renal function tests (creatinine)

3. Tissue diagnosis:

   • Biopsy of the most accessible involved site, typically transbronchial biopsy of hilar lymph nodes 2
   • Histopathology should show non-caseating granulomas 4
   • Special stains and cultures to exclude infectious causes 1

Differential Diagnosis

• Tuberculosis or fungal infections
• Lymphoma
• Berylliosis
• IgG4-related disease
• Vasculitides (especially granulomatosis with polyangiitis)
• Common variable immunodeficiency 1, 2

Treatment Approach

First-line Therapy

• Systemic corticosteroids: Prednisone 20-40 mg daily for 4-6 weeks, followed by gradual taper over 6-12 months 2, 3
• This regimen has been shown to effectively reduce granulomatous inflammation and normalize calcium metabolism 3

Management of Specific Manifestations

1. Vitamin D and calcium abnormalities:

   • Avoid vitamin D supplementation initially as it may worsen dysregulated calcium metabolism 5
   • Monitor calcium levels closely during treatment 3
   • Hydration is important, especially if hypercalcemia develops 3

2. Anemia and elevated WBC:

   • These typically improve with treatment of the underlying sarcoidosis
   • Monitor complete blood count during follow-up

3. Renal function:

   • Assess for renal involvement (present in up to 42% of patients with sarcoidosis-associated hypercalcemia) 5
   • Renal function typically improves with treatment of hypercalcemia and underlying sarcoidosis 6

Second-line Therapy

For patients who fail to respond to corticosteroids or develop significant side effects:

• Methotrexate
• Azathioprine
• Anti-TNF agents (infliximab) for refractory cases 2

Monitoring and Follow-up

• Chest imaging every 3-6 months initially
• Serial calcium levels and renal function tests
• Vitamin D levels (both 25-OH and 1,25-OH)
• Pulmonary function tests if respiratory symptoms are present

Common Pitfalls to Avoid

1. Misdiagnosis: Failure to exclude other granulomatous diseases, particularly infections 2
2. Over-reliance on ACE levels: While often elevated, ACE is neither sensitive nor specific enough for diagnosis 2
3. Inappropriate vitamin D supplementation: Can worsen calcium metabolism in sarcoidosis 5
4. Inadequate follow-up: Sarcoidosis can affect multiple organ systems over time, requiring comprehensive monitoring 2
5. Missing atypical presentations: Not all patients present with the classic findings; sarcoidosis should be considered even without bilateral hilar lymphadenopathy 7

The diagnosis of sarcoidosis requires a compatible clinical presentation, histopathologic evidence of non-caseating granulomas, and exclusion of alternative causes. With appropriate treatment, most patients show significant improvement in symptoms and laboratory abnormalities.