What is the best treatment approach for a patient with hidradenitis suppurativa and mast cell activation syndrome?

Hidradenitis Suppurativa and Mast Cell Activation Syndrome: Treatment Approach

Understanding the Connection

The presence of mast cell activation in hidradenitis suppurativa (HS) represents a critical pathogenic mechanism that should guide treatment selection, particularly favoring IL-17 targeted therapies when biologics are indicated. Recent evidence demonstrates that IL-17A+ mast cells are significantly elevated in HS lesions, especially in advanced Hurley stages, and these cells directly interact with keratinocytes to drive disease pathology 1. This finding is particularly relevant when managing patients with concurrent mast cell activation syndrome (MCAS), as both conditions share inflammatory pathways involving mast cell degranulation and cytokine release 1.

The density of IL-17A+ mast cells increases with disease severity in HS, with the highest concentrations found in Hurley Stage III disease 1. These mast cells maintain close contact with IL-17 receptor A (IL-17RA)-expressing keratinocytes, creating a pathogenic feedback loop that perpetuates inflammation 1.

Treatment Algorithm Based on Disease Severity

Mild Disease (Hurley Stage I)

Start with topical clindamycin 1% solution or gel applied twice daily to all affected areas for 12 weeks 2, 3. This remains first-line therapy regardless of MCAS status, as it addresses the bacterial colonization component without triggering mast cell degranulation 2.

• Combine with benzoyl peroxide wash or chlorhexidine 4% wash daily to reduce Staphylococcus aureus resistance risk 2
• Add intralesional triamcinolone 10 mg/mL (0.2-2.0 mL) for acutely inflamed nodules, which provides rapid symptom relief within 1 day 2, 4
• Avoid topical irritants like resorcinol 15% cream in MCAS patients, as irritant dermatitis may trigger mast cell degranulation 2

Moderate Disease (Hurley Stage II)

For patients with MCAS, proceed directly to clindamycin 300 mg twice daily plus rifampicin 300-600 mg daily for 10-12 weeks rather than tetracyclines 2, 3. This combination achieves response rates of 71-93% and avoids the prolonged antibiotic exposure of tetracycline monotherapy 2.

• Tetracyclines (doxycycline 100 mg twice daily or tetracycline 500 mg twice daily) show only 30% abscess reduction and are less effective for deep inflammatory lesions 2
• The clindamycin-rifampicin combination is superior for abscesses and inflammatory nodules characteristic of Hurley Stage II 2
• Reassess at 12 weeks using pain VAS score, inflammatory lesion count, and DLQI 2, 3
• Consider treatment breaks after 10-12 weeks to limit antimicrobial resistance 2

Severe or Refractory Disease (Hurley Stage III or Failed Antibiotics)

In patients with concurrent HS and MCAS, prioritize IL-17 targeted biologics (secukinumab or bimekizumab) over TNF inhibitors when possible, given the central role of IL-17A+ mast cells in HS pathogenesis 1, 5. However, adalimumab remains the only FDA-approved first-line biologic for moderate-to-severe HS 2, 3.

First-Line Biologic Approach:

• Adalimumab: 160 mg subcutaneous at week 0,80 mg at week 2, then 40 mg weekly (not every other week) starting at week 4 2, 3
• HiSCR response rates: 42-59% at week 12 2
• Treatment with adalimumab reduces IL-17A+ mast cell density in affected tissues 1

Second-Line Biologic Options After Adalimumab Failure:

• Secukinumab (IL-17A inhibitor): Response rates of 64.5-71.4% in adalimumab-failure patients at 16-52 weeks 2
  • Particularly rational choice in MCAS patients given direct targeting of IL-17A+ mast cells 1
  • Brodalumab (IL-17RA inhibitor) also reduces IL-17A+ mast cell numbers and disease severity 1
• Infliximab (TNF inhibitor): 5 mg/kg at weeks 0,2,6, then every 2 months 2, 3
• Ustekinumab (IL-12/23 inhibitor): Alternative pathway targeting 2

Critical Considerations for MCAS Patients

Mast Cell Stabilization

While not specifically addressed in HS guidelines, patients with documented MCAS should continue their baseline mast cell stabilization therapy (H1/H2 antihistamines, cromolyn sodium, leukotriene inhibitors) throughout HS treatment to prevent disease flares triggered by mast cell degranulation.

Avoid Mast Cell Triggers

• Screen for and eliminate known MCAS triggers (heat, friction, certain medications) that may exacerbate HS lesions 6
• Use fragrance-free, hypoallergenic wound dressings for draining lesions 2
• Avoid NSAIDs for pain management if they trigger MCAS symptoms; consider acetaminophen or low-dose opioids instead 2

Corticosteroid Use

Reserve oral prednisone only for acute, widespread HS flares while awaiting biologic response 7, 2. In MCAS patients, short-term corticosteroids may provide dual benefit by suppressing both HS inflammation and mast cell activation, but long-term use is contraindicated 7.

• Prednisone dosing: typically 0.5-1 mg/kg daily for 1-2 weeks maximum 7
• If dose exceeds 15 mg daily for ≥4 weeks, annual TB screening is mandatory 7

Surgical Considerations

Radical surgical excision remains necessary for extensive disease with sinus tracts and scarring when medical therapy fails 2, 4. In MCAS patients, surgical planning requires additional considerations:

• Preoperative mast cell stabilization to prevent perioperative anaphylaxis
• Post-operative antibiotic prophylaxis: clindamycin 300 mg twice daily plus rifampicin 300-600 mg daily for 10-12 weeks 2
• Combining adalimumab with surgery yields greater clinical effectiveness than adalimumab monotherapy 2
• Non-recurrence rates after wide excision: 81.25% 2

Mandatory Adjunctive Measures

Regardless of disease severity or MCAS status, address the following 2, 3:

• Smoking cessation referral: Tobacco worsens HS outcomes 2, 3
• Weight management: Obesity negatively influences disease activity and burden 2, 6
• Screen for depression/anxiety: HS significantly reduces quality of life and promotes psychiatric comorbidity 2, 6
• Screen for cardiovascular risk factors: Measure BP, lipids, HbA1c 2
• Screen for inflammatory bowel disease: Common comorbidity with shared inflammatory pathways 5

Treatment Monitoring

• Assess response at 12 weeks using HiSCR (≥50% reduction in abscess/nodule count with no increase in abscesses or draining fistulas) 2, 3
• Monitor pain VAS scores and DLQI 2, 3
• For adalimumab, if no clinical response after 16 weeks, escalate to second-line biologics 2, 3

Critical Pitfalls to Avoid

• Never use adalimumab 40 mg every other week - this dosing is ineffective for HS 2
• Never use doxycycline or tetracycline monotherapy as first-line for Hurley Stage II with abscesses - these show minimal effect on deep inflammatory lesions 2
• Never use topical clindamycin alone for Hurley Stage II - it only reduces superficial pustules, not inflammatory nodules 2
• Never continue antibiotics long-term without treatment breaks - this increases antimicrobial resistance risk 2
• Never delay biologic therapy in severe disease - early intervention prevents irreversible skin damage with tunnel formation and scarring 5