What is the diagnosis and treatment for a patient with biopsy results showing granulomatous inflammation, perineural infiltration, and acid-fast bacilli?

Leprosy (Hansen's Disease)

The diagnosis is leprosy (Hansen's disease), specifically tuberculoid or borderline tuberculoid leprosy, and treatment should be initiated with multidrug therapy consisting of rifampin 600 mg monthly (supervised), dapsone 100 mg daily, and consideration of a third agent for borderline cases. 1

Diagnostic Confirmation

The triad of granulomatous inflammation, perineural infiltration, and acid-fast bacilli is pathognomonic for leprosy 2, 3:

• Granulomatous inflammation with epithelioid cells and lymphocytes is characteristic of tuberculoid leprosy 1, 4
• Perineural infiltration is the hallmark histologic feature that distinguishes leprosy from other mycobacterial infections—acid-fast bacilli within Schwann cells of peripheral nerves is pathognomonic 2, 3
• Acid-fast bacilli (Mycobacterium leprae) are best visualized with Fite-Faraco staining, though they may be sparse or absent in tuberculoid forms 4, 2

The presence of caseating necrosis with giant cell formation supports tuberculoid leprosy, whereas noncaseating granulomas would suggest borderline forms 1. This contrasts with tuberculous infections where disc spaces are typically involved and paraspinal abscesses are common 1.

Classification and Clinical Correlation

Determine the leprosy classification based on additional histologic features 1:

• Tuberculoid leprosy: Few well-demarcated lesions with anesthesia, peripheral nerve swelling, and sparse bacilli 1
• Borderline tuberculoid: Features of both forms with moderate bacillary load 4
• Lepromatous leprosy: Multiple symmetric lesions, numerous bacilli, and bilateral distribution 1
• Indeterminate leprosy: Early hypopigmented lesions without developed features, though bacilli can be found in dermis before nerve invasion 5

Treatment Protocol

For Tuberculoid and Indeterminate Disease

Initiate paucibacillary multidrug therapy 6:

• Rifampin 600 mg monthly (supervised administration) 6
• Dapsone 100 mg daily (50 mg starting dose, titrated up; correspondingly smaller doses in children) 6
• Continue treatment for 6 months of rifampin with dapsone continued until all clinical activity is controlled, then an additional 3 years for tuberculoid and 5 years for borderline tuberculoid patients 6

For Borderline Tuberculoid Disease

Consider adding a third agent 6:

• Clofazimine 50-100 mg daily or Ethionamide 250-500 mg daily may be co-administered 6
• Treatment duration extends to ensure complete clinical resolution 6

For Lepromatous and Borderline Lepromatous Disease

Initiate multibacillary multidrug therapy 6:

• Rifampin 600 mg daily for 2 years (or 600 mg monthly if supervised under WHO protocol) 6
• Dapsone 100 mg daily continued for 3-10 years until clinical activity controlled with negative skin scrapings and biopsies for 1 year 6
• Third agent (clofazimine or ethionamide) should be added 6
• After achieving control, continue dapsone for an additional 10 years for borderline patients and for life for lepromatous patients 6

Critical Management Considerations

Monitoring for Treatment Response

• Nerve biopsy is valuable for evaluating treatment effectiveness, as bacilli may persist in nerves despite skin negativity 7
• Ultrastructural studies are important for recognizing bacilli that may lose acid-fast resistance during treatment 7
• Serial examinations should assess for new lesions, nerve function, and signs of relapse 6

Detecting Dapsone Resistance

Suspect secondary dapsone resistance when 6:

• Lepromatous or borderline lepromatous patients relapse clinically and bacteriologically during regular dapsone therapy
• Solid staining bacilli appear in new active lesions
• No response occurs within 3-6 months of supervised therapy with assured compliance
• If resistance is confirmed, switch to alternative drugs and consider mouse footpad sensitivity testing (available through USPHS Carville) 6

Vascular Complications

Be vigilant for vascular lesions that may cause focal nerve infarcts 7:

• Endoneurial inflammation can compress vessels leading to small focal infarcts 7
• Endoneurial lymphocytic vasculitis may occur 7
• These vascular complications can accelerate nerve damage and require aggressive management 7

Common Diagnostic Pitfalls

Leprosy can masquerade as other conditions, particularly in non-endemic regions 2:

• May present clinically and histologically as granuloma annulare with palisaded granulomas and necrobiosis 2
• The key diagnostic clue is perineural lymphocytes in any granulomatous infiltrate—this should always prompt Fite staining 2
• Pure neuritic leprosy presents without cutaneous lesions, causing peripheral neuropathy that may be misdiagnosed 3
• In early indeterminate disease, extensive serial sections (145+ sections) may be needed to identify sparse bacilli 5

PCR for M. leprae DNA can be valuable when acid-fast staining is negative but clinical suspicion remains high 4.