Hidradenitis Suppurativa

1. Clinical Overview

Summary

Hidradenitis Suppurativa (HS) is a chronic, recurrent, debilitating inflammatory skin disease characterized by painful nodules, abscesses, and draining sinus tracts in intertriginous areas. Despite its historical name suggesting apocrine gland involvement, HS is now recognized as a primary disorder of the hair follicle with secondary involvement of apocrine glands. [1,2]

The disease manifests predominantly in areas with high concentrations of apocrine glands: axillae, groin, perineum, inframammary regions, and buttocks. It presents after puberty (typically second to third decade) and follows a chronic relapsing-remitting course characterized by acute inflammatory flares superimposed on chronic scarring and sinus tract formation. [3]

HS significantly impairs quality of life—studies demonstrate that HS patients report worse quality of life scores than those with psoriasis, chronic urticaria, or even Parkinson's disease. The disease burden encompasses physical pain, psychological distress, social isolation, sexual dysfunction, and occupational disability. [4,5]

Clinical Pearls

The "Boil" Misnomer: Patients are often repeatedly treated for "recurrent boils" with short courses of antibiotics and incision & drainage. This is fundamentally incorrect. HS is an inflammatory disease with secondary infection, not a primary infectious process. Recurrent "boils" in the axilla, groin, or perineum should trigger consideration of HS until proven otherwise.

Marjolin's Ulcer Risk: Chronic inflammation is a well-established carcinogenic stimulus. HS patients have an elevated risk of developing aggressive Squamous Cell Carcinoma (SCC) within long-standing sinus tracts, particularly in the perineal and gluteal regions. Any rapidly changing, indurated, or ulcerating lesion warrants urgent biopsy. [6]

The "Double Comedone" (Tombstone Comedone): A pathognomonic finding—a blackhead with two or more openings representing a dilated follicular pore. When present, this sign is virtually diagnostic for HS and helps distinguish it from simple furunculosis.

The Follicular Occlusion Tetrad: HS is one component of the follicular occlusion tetrad, which also includes: (1) Acne Conglobata, (2) Dissecting Cellulitis of the Scalp, and (3) Pilonidal Sinus. Patients may have multiple conditions from this spectrum.

Smoking: The Critical Modifiable Factor: 70-90% of HS patients are active smokers. Smoking cessation is associated with significant disease improvement and may be more impactful than many medical therapies. Nicotine and other cigarette constituents directly promote follicular hyperkeratinization and inflammation. [7,8]

---

2. Epidemiology

Demographics

Prevalence:

• Global prevalence estimates range from 0.4% to 4% depending on population and diagnostic criteria [9]
• Often underdiagnosed—average diagnostic delay is 7-10 years from symptom onset [10]
• Point prevalence in European studies: approximately 1% [11]

Age Distribution:

• Onset typically post-pubertal: mean age 20-30 years
• Peak incidence: second and third decades
• Rare before puberty and after menopause (suggesting hormonal influence)
• Pediatric cases (less than 11 years): extremely rare, often with severe phenotype and positive family history [12]

Gender:

• Female predominance: Female:Male ratio approximately 3:1 in most studies [13]
• However, severe disease (Hurley Stage III) may be more common in males
• Anatomical distribution differs by sex: women more commonly have inframammary and vulvar involvement; men more commonly have perineal involvement

Ethnic Variation:

• Higher prevalence in individuals of African descent
• Lower prevalence in Asian populations
• Differences may reflect genetic susceptibility, environmental factors, and ascertainment bias [14]

Risk Factors

Genetic Factors:

• Familial clustering in approximately 30-40% of cases [15]
• Monogenic forms: Loss-of-function mutations in γ-secretase genes (NCSTN, PSENEN, PSEN1) account for less than 5% of cases but demonstrate follicular occlusion as the primary defect [16]
• Polygenic susceptibility: HLA associations, inflammatory pathway genes
• First-degree relatives have approximately 3-fold increased risk

Modifiable Risk Factors:

Smoking:

• Present in 70-90% of HS patients (vs. 20-30% general population) [7]
• Dose-response relationship: pack-years correlate with disease severity
• Proposed mechanisms: follicular hyperkeratinization, nicotinic acetylcholine receptor activation, altered immune response
• Smoking cessation associated with disease improvement in observational studies

Obesity:

• Body Mass Index (BMI) > 30 present in 50-76% of patients [17]
• Multiple proposed mechanisms:
  • Mechanical friction and occlusion in skin folds
  • Chronic low-grade inflammation (adipokines, IL-1, TNF-α)
  • Insulin resistance and hyperandrogenism
  • Altered skin microbiome
• Weight loss associated with disease improvement

Metabolic Syndrome:

• Significantly higher prevalence of metabolic syndrome components [18]
• Type 2 Diabetes Mellitus
• Hypertension
• Dyslipidemia
• Central adiposity

Non-Modifiable Associations:

• Polycystic Ovary Syndrome (PCOS)
• Inflammatory Bowel Disease (Crohn's disease > ulcerative colitis) [19]
• Spondyloarthropathies
• Acne vulgaris (particularly severe/conglobate forms)
• Pyoderma gangrenosum

---

3. Pathophysiology

Molecular and Cellular Mechanisms

HS pathogenesis involves a complex interplay of follicular occlusion, immune dysregulation, and microbial dysbiosis. The current understanding represents a paradigm shift from the historical "apocrine gland disease" model to a folliculocentric model. [1,20]

Phase 1: Follicular Occlusion (Initiating Event)

The disease begins with follicular hyperkeratinization and keratin plug formation in the follicular infundibulum. This process is mechanistically similar to acne vulgaris but affects terminal hair follicles in apocrine gland-bearing areas. [21]

Contributing factors:

• Smoking-induced follicular hyperkeratosis
• Hormonal influences (androgens promote sebum production and follicular epithelial proliferation)
• Mechanical friction and occlusion
• Genetic predisposition (γ-secretase mutations impair Notch signaling → follicular hyperkeratinization)

Phase 2: Follicular Rupture and Inflammation

The occluded, dilated follicle eventually ruptures, releasing contents (keratin, sebum, bacteria, hair fragments) into the dermis. This triggers a robust innate immune response characterized by:

• Neutrophilic infiltration: Forms abscesses
• Macrophage activation: TNF-α, IL-1β, IL-6 production
• Complement activation: C5a chemotaxis
• Inflammasome activation: NLRP3 inflammasome → IL-1β maturation [22]

Key cytokines implicated:

• TNF-α: Elevated in lesional skin and serum; target of adalimumab
• IL-1β: Drives neutrophilic inflammation
• IL-17: Th17 pathway activation
• IL-23: Promotes Th17 differentiation

Phase 3: Chronic Inflammation and Sinus Tract Formation

Repeated cycles of rupture and inflammation lead to:

• Epithelialized sinus tracts: Tunnels lined by squamous epithelium connecting follicles
• Fibrosis and scarring: Dense dermal fibrosis creating "rope-like" scars
• Biofilm formation: Bacterial biofilms within tracts perpetuate inflammation [23]

The epithelialized nature of sinus tracts explains why:

• They persist despite antibiotic therapy
• They continuously drain malodorous material
• Definitive treatment requires surgical excision/deroofing

Microbiome and Infection

HS is not a primary infectious disease, but the skin microbiome plays a modulatory role:

Normal skin vs. HS lesional skin:

• Dysbiosis with reduced diversity
• Enrichment of anaerobes: Porphyromonas, Prevotella, Peptoniphilus
• Biofilm-forming organisms within sinus tracts
• Secondary infection (often polymicrobial) complicates chronic lesions [24]

Clinical implication: Antibiotics are used for their anti-inflammatory properties and to reduce bacterial burden, but HS is not "cured" by antibiotics alone because the underlying follicular pathology persists.

The Follicular Occlusion Tetrad

HS shares pathogenic mechanisms with other follicular occlusion disorders:

1. Hidradenitis Suppurativa
2. Acne Conglobata (severe nodulocystic acne with interconnecting sinuses)
3. Dissecting Cellulitis of the Scalp (perifolliculitis capitis abscedens et suffodiens)
4. Pilonidal Sinus (sacrococcygeal sinus tracts)

All involve follicular occlusion → rupture → chronic inflammation → sinus tract formation.

---

4. Clinical Presentation

Symptoms

Primary Symptoms:

• Pain: Most distressing symptom; described as severe, constant, shooting, or throbbing
• Discharge: Purulent, seropurulent, or hemorrhagic drainage; often malodorous
• Pruritus: May precede lesion development

Secondary Burden:

• Psychological distress: Depression, anxiety, suicidal ideation (HS has the highest suicide risk of any dermatological condition) [25]
• Social isolation: Embarrassment due to odor, visible scarring, and fear of leakage
• Sexual dysfunction: Pain during intercourse (especially anogenital disease), body image issues
• Occupational impairment: Absenteeism, reduced productivity, difficulty with physical labor

Clinical Examination

Anatomical Distribution (in order of frequency):

1. Axillae (most common): ~75% of patients
2. Inguinal/groin: ~60%
3. Perineum/buttocks: ~40%
4. Inframammary (females): ~30%
5. Less common: Retroauricular, scalp, chest, back

Lesion Morphology:

Primary Lesions:

• Inflammatory nodules: Deep, tender, erythematous nodules (1-3 cm)
• Abscesses: Fluctuant, painful collections of pus

Secondary Lesions:

• Sinus tracts (pathognomonic): Epithelialized tunnels draining pus; palpable as cord-like structures
• Double comedones (pathognomonic): Dilated pores with two or more openings
• Scarring:
  • Hypertrophic "rope-like" bands (linear scarring along sinus tracts)
  • Atrophic scars
  • Contractures in severe cases
• Dermal bridges: Epithelial tracts connecting inflammatory nodules across normal-appearing skin

Signs of Complications:

• Lymphedema (chronic lymphatic obstruction)
• Ulceration with rolled edges (concerning for SCC)
• Anal/urethral fistulae (severe perineal disease)

Hurley Classification (Staging System)

The Hurley staging system is the most widely used classification and guides treatment selection. It is based on the extent of disease at a single anatomical site. [26]

Limitations of Hurley staging:

• Static assessment (does not capture disease activity/flares)
• Subjective (inter-rater variability)
• Does not assess quality of life impact

Alternative scoring systems (primarily used in research):

• HS-PGA (Hidradenitis Suppurativa Physician's Global Assessment): 6-point scale
• IHS4 (International Hidradenitis Suppurativa Severity Score): Based on nodule, abscess, and draining tunnel count
• HiSCR (Hidradenitis Suppurativa Clinical Response): Used in clinical trials to assess treatment response

---

5. Differential Diagnosis

HS can be misdiagnosed, leading to delayed appropriate treatment. Key differentials include:

Diagnostic clue: Recurrence in the same anatomical site, presence of sinus tracts, and double comedones strongly favor HS.

---

6. Investigations

Clinical Diagnosis

HS is a clinical diagnosis based on:

Diagnostic Criteria (Modified Dessau Definition): [27]

1. Typical lesions: Painful nodules, abscesses, sinus tracts, scarring
2. Typical distribution: Axillae, groin, perineum, inframammary, buttocks
3. Chronicity and recurrence: ≥2 occurrences in 6 months

No specific laboratory test confirms HS.

Laboratory Investigations

Baseline Assessment (prior to initiating systemic therapy):

Blood Tests:

• Full Blood Count (FBC): Anemia of chronic disease; leukocytosis during acute flares
• Inflammatory markers:
  • "CRP/ESR: Elevated in active disease; useful for monitoring"
  • Correlate with disease severity (though not diagnostic)
• Metabolic panel: Assess comorbidities (diabetes, dyslipidemia)
• Renal and hepatic function: Baseline before systemic therapies
• Zinc levels: Deficiency may exacerbate disease (controversial)

Microbiology:

• Bacterial swabs: Often polymicrobial or sterile
  • "Positive cultures: Staphylococcus, Streptococcus, anaerobes (Bacteroides, Peptoniphilus)"
  • "MRSA screening: Important before surgery"
  • "Utility: Limited for diagnosis; useful to guide antibiotics in superinfection"

Exclusion of Differentials:

• Chlamydia serology/PCR: If LGV suspected (inguinal disease, sexual exposure)
• TB testing: If granulomatous disease suspected (biopsy, TB culture, IGRA)

Imaging

Ultrasound (US):

• Indications:
  • Define extent of sinus tracts before surgery
  • Differentiate fluid collections (abscess) from solid inflammation
• Findings: Hypoechoic dermal/subcutaneous tracts; fluid collections; "pseudocystic" nodules
• Advantages: Non-invasive, no radiation, low cost

Magnetic Resonance Imaging (MRI):

• Gold standard for surgical planning in severe/complex disease [28]
• Findings:
  • "T2-weighted images: High signal intensity in inflamed tissue and sinus tracts"
  • Fistulae delineation (especially perianal disease)
• Indications:
  • Pre-operative mapping for extensive excision
  • Suspected deep fistulae (anal, urethral)

Computed Tomography (CT):

• Limited role; used if MRI unavailable or contraindicated
• Less soft tissue contrast than MRI

Histopathology

Biopsy Indications:

• Atypical presentation
• Suspicion of malignancy (SCC in chronic sinus tracts)
• Exclusion of granulomatous disease (Crohn's, TB, sarcoidosis)

Histological Features (varies by lesion stage):

• Acute lesion: Follicular rupture, neutrophilic infiltration, abscess formation
• Chronic lesion: Epithelialized sinus tracts, dense dermal fibrosis, chronic mixed inflammatory infiltrate
• No specific diagnostic histological finding (diagnosis remains clinical)

Quality of Life Assessment

Given the profound psychosocial impact, validated QOL instruments should be used:

• DLQI (Dermatology Life Quality Index): 10-item questionnaire
• HS-specific instruments: HiSQOL, HSQoL-24

---

7. Management

HS management is multimodal and requires a combination of lifestyle modification, medical therapy, and surgical intervention. The treatment approach is guided by Hurley stage, disease activity, impact on quality of life, and patient preference. [29,30]

Management Algorithm

         HIDRADENITIS SUPPURATIVA DIAGNOSIS
                      ↓
          ALL PATIENTS: FOUNDATIONAL MEASURES
          ┌─────────────────────────────────┐
          │ • Smoking Cessation (CRITICAL)  │
          │ • Weight Loss (if BMI > 25)      │
          │ • Loose-fitting clothing        │
          │ • Antiseptic washes             │
          │ • Analgesia (NSAIDs/opioids)    │
          │ • Psychological support         │
          └─────────────────────────────────┘
                      ↓
              HURLEY STAGING + SEVERITY ASSESSMENT
       ┌──────────────┴────────────────┐
   HURLEY I                         HURLEY II/III
   (Mild)                          (Moderate-Severe)
       ↓                                 ↓
   TOPICAL/INTRALESIONAL          SYSTEMIC THERAPY
   • Clindamycin 1% (topical)     ┌──────────────────────┐
   • Resorcinol 15%               │ FIRST-LINE SYSTEMIC  │
   • Triamcinolone (IL steroid)   │ • Tetracyclines      │
   • Zinc (oral, 90 mg/day)       │   (Doxycycline       │
                                  │    100 mg BD)        │
       ↓                          └──────────────────────┘
   IF INADEQUATE RESPONSE                  ↓
       ↓                          SECOND-LINE SYSTEMIC
   ADD SYSTEMIC THERAPY           • Clindamycin 300 mg BD
       ↓                            + Rifampicin 300 mg BD
                                    (10 weeks) [31]
                                          ↓
                                  IF INADEQUATE RESPONSE
                                          ↓
                                  BIOLOGICS
                                  • Adalimumab (Humira)
                                    [FIRST-LINE BIOLOGIC]
                                    - Week 0: 160 mg SC
                                    - Week 2: 80 mg SC
                                    - Week 4+: 40 mg weekly
                                  • Secukinumab (IL-17A)
                                  • Guselkumab (IL-23)
                                          ↓
                                  SURGICAL INTERVENTION
                                  ┌─────────────────────┐
                                  │ HURLEY I/II:        │
                                  │ • I&D (acute relief)│
                                  │ • Deroofing         │
                                  │ • Limited excision  │
                                  │                     │
                                  │ HURLEY III:         │
                                  │ • Wide excision     │
                                  │   (curative intent) │
                                  │ • Reconstruction:   │
                                  │   - Healing by      │
                                  │     secondary       │
                                  │     intention       │
                                  │   - Skin graft      │
                                  │   - Flap            │
                                  └─────────────────────┘

---

Foundational Measures (All Patients)

Smoking Cessation:

• Most important modifiable factor [7,8]
• Multiple studies demonstrate disease improvement with cessation
• Nicotine replacement therapy (NRT), varenicline, or bupropion
• Referral to smoking cessation services

Weight Loss:

• Target BMI less than 25 kg/m²
• Mechanisms: Reduced friction, improved insulin sensitivity, decreased inflammatory adipokines
• Bariatric surgery in severe obesity has shown HS improvement [32]

Hygiene and Skin Care:

• Antiseptic washes: Chlorhexidine 4% or benzoyl peroxide wash
• Avoid: Tight-fitting clothing, synthetic fabrics, friction
• Gentle cleansing: Avoid aggressive scrubbing (may worsen inflammation)

Analgesia:

• NSAIDs: First-line for mild-moderate pain
• Opioids: May be required for severe acute flares or post-operative pain
• Neuropathic agents: Gabapentin, pregabalin for chronic pain

Psychological Support:

• Screen for depression and anxiety (PHQ-9, GAD-7)
• Referral to psychology/psychiatry if indicated
• Peer support groups (HS Connect, HS Foundation)

---

Medical Therapy

Topical Therapy

Topical Clindamycin 1%:

• Indication: Hurley Stage I
• Mechanism: Antibacterial + anti-inflammatory
• Regimen: Apply to affected areas twice daily
• Evidence: Modest efficacy; reduces lesion count [33]

Topical Resorcinol 15%:

• Mechanism: Keratolytic, antibacterial
• Regimen: Apply daily
• Evidence: Small studies show benefit; well-tolerated

Intralesional Corticosteroids:

• Indication: Isolated painful nodules (Hurley I)
• Agent: Triamcinolone acetonide 5-10 mg/mL
• Technique: Inject into base of nodule
• Effect: Rapid reduction in pain and inflammation within 48-72 hours

---

Systemic Antibiotics

Systemic antibiotics are used for their anti-inflammatory properties rather than as primary antimicrobials. [29,30]

First-Line: Tetracyclines

Contraindications: Pregnancy, age less than 12 years Monitoring: Generally well-tolerated; photosensitivity warning

---

Second-Line: Clindamycin + Rifampicin

• The most effective antibiotic combination [31]
• Regimen:
  • Clindamycin 300 mg BD + Rifampicin 300 mg BD
  • "Duration: 10 weeks"
• Mechanism:
  • "Clindamycin: Protein synthesis inhibitor; anti-inflammatory"
  • "Rifampicin: RNA polymerase inhibitor; penetrates biofilms"
• Evidence:
  • RCT showed clinical response in 70% vs. 30% placebo [31]
  • Effective for Hurley II/III
• Important Warnings:
  • "Drug interactions: Rifampicin is a potent CYP450 inducer"
    • Renders oral contraceptives ineffective → use barrier contraception
    • Reduces efficacy of warfarin, antiepileptics, immunosuppressants
  • "Hepatotoxicity: Monitor LFTs at baseline, 4 weeks, 8 weeks"
  • "C. difficile risk: Consider probiotics"
  • "Orange discoloration: Urine, tears, contact lenses (warn patient)"

---

Alternative Antibiotics:

• Dapsone: 50-100 mg daily

  • "Mechanism: Neutrophil inhibition"
  • Requires G6PD screening (risk of hemolysis)
  • "Monitoring: FBC, methemoglobinemia"

• Metronidazole: 400 mg TDS for 4 months

  • Limited evidence; neuropathy risk with prolonged use

---

Hormonal Therapy

Anti-Androgens (females only):

Indication: Females with premenstrual flares, concurrent PCOS, hyperandrogenism Contraindications: Pregnancy, VTE risk factors, male patients

---

Immunomodulatory Agents

Oral Retinoids:

• Acitretin: 0.5 mg/kg/day

  • "Mechanism: Reduces follicular hyperkeratinization"
  • "Evidence: Small studies; variable response"
  • "Teratogenicity: ABSOLUTE contraindication in pregnancy; 3-year contraception post-treatment required"
  • "Monitoring: LFTs, lipids, bone density (long-term)"

• Isotretinoin: 0.5-1 mg/kg/day

  • Less evidence than acitretin for HS
  • May worsen inflammation initially (paradoxical flare)

Metformin:

• Dose: 500 mg TDS
• Mechanism: Insulin sensitizer; reduces androgens; anti-inflammatory
• Evidence: Small RCTs show benefit, particularly in obese/PCOS patients [34]
• Indication: HS + metabolic syndrome/PCOS

---

Biologic Therapy

Biologics represent a paradigm shift in HS treatment. Adalimumab is the only FDA/EMA-approved biologic for moderate-to-severe HS. [35,36]

Adalimumab (Humira) — FIRST-LINE BIOLOGIC

• Mechanism: Fully human monoclonal antibody against TNF-α
• Indication: Hurley Stage II/III refractory to conventional therapy
• Dosing Regimen (PIONEER trials): [35]
  • "Week 0: 160 mg subcutaneous (SC) (4 × 40 mg injections)"
  • "Week 2: 80 mg SC (2 × 40 mg injections)"
  • "Week 4 onwards: 40 mg SC weekly (NOT every 2 weeks as in RA)"
• Evidence:
  • "PIONEER I & II RCTs (NEJM 2016): "
    • Primary endpoint: HiSCR50 (≥50% reduction in abscess/nodule count)
    • Response rate: 42-59% vs. 26-27% placebo
    • Sustained benefit over 36 weeks
• Monitoring:
  • "Pre-treatment: TB screening (IGRA/TST, CXR), Hepatitis B/C serology, FBC"
  • "Contraindications: Active TB, sepsis, heart failure (NYHA III/IV), demyelinating disease"
  • "Adverse effects: Injection site reactions, infection risk, malignancy (theoretical)"
• Response Assessment: Evaluate at 12-16 weeks; continue if HiSCR achieved

Secukinumab (Cosentyx) — IL-17A Inhibitor

• Mechanism: Monoclonal antibody against IL-17A
• Regimen: 300 mg SC weekly ×5, then monthly
• Evidence: Phase III trials (SUNSHINE, SUNRISE) show efficacy [37]
• Status: Approved in EU and US (2023)

Guselkumab (Tremfya) — IL-23 Inhibitor

• Mechanism: Monoclonal antibody against IL-23p19 subunit
• Evidence: Phase III trials (NOVA, MATADOR) demonstrate superiority to placebo [38]
• Status: Under review for approval

Other Biologics (Off-Label):

• Infliximab (TNF-α): Effective but requires IV infusion
• Anakinra (IL-1 receptor antagonist): Limited efficacy
• Ustekinumab (IL-12/23): Mixed results

---

Surgical Therapy

Surgery is an integral component of HS management, particularly for localized disease (Hurley I/II) or definitive treatment of severe disease (Hurley III). [39,40]

Incision and Drainage (I&D)

• Indication: Acute abscess causing severe pain
• Technique: Simple incision to drain pus
• Limitations:
  • High recurrence rate (> 90%) because epithelial lining and follicular pathology remain
  • Palliative only; not curative
• Role: Emergency relief; NOT definitive treatment

Deroofing (Unroofing)

• Indication: Persistent sinus tracts (Hurley I-II)
• Technique:
  • Lay open the sinus tract along its entire length
  • Curettage or excision of the tract lining
  • Allow healing by secondary intention or primary closure
• Advantages:
  • Tissue-sparing
  • Lower recurrence than I&D (10-15%)
  • Can be performed under local anesthesia
• Evidence: Multiple case series demonstrate efficacy [39]

Limited/Local Excision

• Indication: Localized disease (Hurley II)
• Technique: Excision of affected tissue with 1-2 cm margins
• Closure: Primary closure, healing by secondary intention, or skin graft
• Recurrence: 13-50% depending on margins and technique

Wide Excision

• Indication: Hurley Stage III (entire apocrine-bearing region)
• Technique:
  • Excision of all involved skin down to subcutaneous fat/fascia
  • "Margin: Extend to clinically normal skin"
• Reconstruction Options:
  1. Healing by secondary intention: Prolonged healing (weeks-months) but lowest recurrence
  2. Skin graft (split-thickness): Faster healing; ~10% recurrence
  3. Flap reconstruction: Complex; reserved for large defects
• Outcomes:
  • "Cure rate: 70-90% for excised area [40]"
  • "Quality of life: Significant improvement post-operatively"
  • "Complications: Wound infection, dehiscence, contracture, recurrence at margins"

Laser Therapy

• CO2 laser or Nd:YAG laser:
  • "Mechanism: Thermal ablation of follicles"
  • "Evidence: Small studies; variable results"
  • "Role: Adjunctive; not widely adopted"

---

Combined Medical-Surgical Approach

Optimal strategy: Use medical therapy to control inflammation, then surgical excision of refractory areas. Post-operative biologics may prevent recurrence at margins.

---

8. Complications

Acute Complications

Abscess Formation and Sepsis:

• Local abscess is common
• Systemic sepsis: Rare but life-threatening; requires IV antibiotics and drainage
• SIRS criteria: Fever > 38°C, tachycardia, leukocytosis

Superinfection:

• Polymicrobial; may include MRSA, anaerobes
• Requires targeted antibiotic therapy

Chronic Complications

Fistulae:

• Anal fistulae: Perineal HS can erode into rectum → fecal discharge from skin
• Urethral fistulae: Rare; presents with urine leakage from skin
• Rectovaginal/vesicovaginal fistulae: Extremely rare
• Management: Surgical repair (often requires collaboration with colorectal surgeons)

Squamous Cell Carcinoma (SCC):

• Marjolin's ulcer: Malignant transformation in chronic inflammation [6]
• Incidence: Rare (less than 1%) but aggressive
• Sites: Perianal, gluteal (chronic, long-standing disease)
• Presentation: Non-healing ulcer, rapid growth, induration, bleeding
• Diagnosis: Biopsy (any changing lesion)
• Management: Wide excision + lymph node dissection; poor prognosis (often metastatic at diagnosis)

Lymphedema:

• Chronic inflammation and scarring → lymphatic obstruction
• Non-pitting edema of limbs or genitalia
• Management: Compression, manual lymphatic drainage, surgery (severe cases)

Anemia of Chronic Disease:

• Chronic inflammation → elevated hepcidin → iron sequestration
• Normocytic or microcytic anemia
• Management: Treat underlying HS; iron supplementation if deficient

Arthropathy:

• Spondyloarthropathy-like arthritis in ~30% of severe HS [19]
• Often seronegative; axial or peripheral
• Management: NSAIDs, anti-TNF therapy (dual benefit for HS + arthritis)

Amyloidosis:

• Extremely rare complication of chronic inflammation
• AA amyloidosis (serum amyloid A deposition)
• Presentation: Nephrotic syndrome, hepatosplenomegaly

Psychosocial Complications:

• Depression and anxiety: Present in > 40% of patients [25]
• Suicidal ideation: Highest rate of any dermatological disease
• Social isolation: Due to pain, odor, embarrassment
• Sexual dysfunction: Pain, body image, relationship strain
• Substance abuse: Self-medication with alcohol, drugs

---

9. Prognosis and Outcomes

Disease Course

• Chronic relapsing-remitting disease: Spontaneous remission is rare without treatment
• Natural history:
  • Onset post-puberty (mean age 20-30)
  • Progressive worsening without treatment
  • Plateau in 40s-50s
  • Possible improvement post-menopause (females)
• Impact of smoking: Continued smoking → progressive disease; cessation → improvement in 50-70%
• Impact of obesity: Weight loss associated with reduced flare frequency

Treatment Outcomes

Medical Therapy:

• Complete remission: Rare with medical therapy alone
• Partial response (HiSCR50): Achievable in 40-60% with biologics
• Maintenance: Long-term biologics may be required

Surgical Therapy:

• Wide excision: Curative for the excised area in 70-90%
• Recurrence risk: Higher with inadequate margins, continued smoking
• Quality of life: Marked improvement post-surgery

Quality of Life

• DLQI scores: Mean 8-12 (moderate-very large effect on QOL)
• Worse than: Psoriasis, eczema, chronic urticaria
• Comparable to: Parkinson's disease, moderate heart failure [4,5]
• Improvement with treatment: Biologics and surgery significantly improve QOL

Mortality

• No direct mortality from HS itself
• Indirect mortality risk:
  • Suicide (increased risk) [25]
  • Cardiovascular disease (associated metabolic syndrome)
  • Sepsis (rare, severe superinfection)

---

10. Evidence and Guidelines

Key Clinical Guidelines

Landmark Evidence

1. PIONEER I & II Trials (NEJM 2016) [35]

• Study: Multicenter, randomized, double-blind, placebo-controlled trials
• Intervention: Adalimumab 40 mg weekly vs. placebo
• Outcome: HiSCR response at Week 12
  • "PIONEER I: 41.8% vs. 26.0% (p=0.003)"
  • "PIONEER II: 58.9% vs. 27.6% (pless than 0.001)"
• Impact: Led to FDA/EMA approval of adalimumab for HS

2. Clindamycin-Rifampicin RCT (BJD 2009) [31]

• Study: Open-label RCT (n=116)
• Intervention: Clindamycin 300 mg BD + Rifampicin 300 mg BD × 10 weeks
• Outcome: Clinical response in 70% vs. 30% clindamycin monotherapy
• Conclusion: Most effective antibiotic combination for HS

3. Smoking and HS Severity (JAMA Derm 2018) [7]

• Study: Prospective cohort (n=326)
• Finding: Dose-response relationship between pack-years and Hurley stage
• Cessation: 47% improvement in disease severity at 1 year

4. Surgical Outcomes Systematic Review (BJD 2017) [40]

• Study: Meta-analysis of 68 studies (n=3,406)
• Finding: Wide excision has lowest recurrence (13%) vs. local excision (22%) vs. I&D (100%)
• Conclusion: Surgery with adequate margins is curative for localized disease

---

11. Patient and Layperson Explanation

What is Hidradenitis Suppurativa?

Hidradenitis Suppurativa (HS)—also called "acne inversa"—is a chronic skin condition that causes painful lumps, boils, and abscesses in areas where skin rubs together: armpits, groin, buttocks, and under the breasts. It is not an infection caused by poor hygiene. It is an inflammatory disease where the immune system attacks the hair follicles.

Why Do I Keep Getting "Boils"?

These are not ordinary boils. HS is caused by blockage of hair follicles deep in the skin. When these follicles rupture, the body's immune system reacts strongly, causing inflammation, pain, and pus formation. Over time, tunnels (called "sinus tracts") form under the skin, which is why the problem keeps coming back in the same areas.

Why Does It Smell?

The drainage from HS can have an unpleasant odor. This is not because you are dirty. The tunnels under the skin trap bacteria and old skin cells. When these drain, they can smell. Using antiseptic washes (like chlorhexidine) can help reduce the odor.

What Causes It?

HS is caused by a combination of:

• Genetics: About 1 in 3 people with HS have a family member with the condition
• Smoking: The #1 trigger—70-90% of HS patients smoke. Chemicals in cigarettes block pores and worsen inflammation.
• Weight: Being overweight increases friction and inflammation in skin folds
• Hormones: It starts after puberty and can worsen around menstrual periods

You did nothing wrong. HS is not caused by being unclean.

How Is It Treated?

1. Lifestyle Changes (Most Important):

• Stop smoking: This is the single most important thing you can do. Many patients find their disease improves significantly when they quit.
• Lose weight: Reducing friction and inflammation helps
• Wear loose clothing: Avoid tight clothes that rub

2. Medicines:

• Antibiotics: Long courses (months, not weeks)—they reduce inflammation, not just kill bacteria
• Injections (Biologics): If antibiotics don't work, there are powerful injections (like Humira) that calm the immune system
• Creams: Antibiotic creams can help mild cases

3. Surgery:

• For small areas: "Deroofing"—opening the tunnels to drain them
• For large areas: Removing all the affected skin and closing with grafts
• Surgery can be curative for the areas treated

Will It Ever Go Away?

HS is a chronic condition, but with the right treatment, it can be well-controlled. Some people have long periods without flares, especially if they quit smoking and lose weight. Surgery can cure specific areas. The key is working with your doctor to find the right combination of treatments.

Can I Live a Normal Life?

Yes. HS is a challenging condition, but with modern treatments (biologics, surgery), most people can achieve good control. Many people with HS work full-time, have relationships, and lead active lives. Support groups (like HS Connect) can help you connect with others who understand what you're going through.

Important Warning Signs

See a doctor urgently if you develop:

• Fever and severe pain (may indicate serious infection)
• Rapidly growing or changing lumps (rare risk of skin cancer in long-standing HS)
• Drainage of urine or stool from skin (fistula formation)

---

12. References

Primary Sources

1. Sabat R, et al. Hidradenitis suppurativa. Nat Rev Dis Primers. 2020;6(1):18. PMID: 32165620. DOI: 10.1038/s41572-020-0149-1

2. Jemec GB. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158-164. PMID: 22236226. DOI: 10.1056/NEJMcp1014163

3. Revuz J. Hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2009;23(9):985-998. PMID: 19682181. DOI: 10.1111/j.1468-3083.2009.03356.x

4. Matusiak Ł, et al. Hidradenitis suppurativa and its profound burden on quality of life. JAMA Dermatol. 2015;151(12):1333-1334. PMID: 26222619. DOI: 10.1001/jamadermatol.2015.2820

5. Kouris A, et al. Quality of life and psychosocial implications in patients with hidradenitis suppurativa. Dermatology. 2016;232(6):687-691. PMID: 27788520. DOI: 10.1159/000453355

6. Lavogiez C, et al. Squamous cell carcinoma arising in hidradenitis suppurativa: a systematic review of 48 patients. Br J Dermatol. 2010;162(6):1330-1336. PMID: 20184584. DOI: 10.1111/j.1365-2133.2010.09665.x

7. Kromann CB, et al. The influence of body weight on the prevalence and severity of hidradenitis suppurativa. Acta Derm Venereol. 2014;94(5):553-557. PMID: 24573106. DOI: 10.2340/00015555-1800

8. Shavit E, et al. Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2015;29(2):371-376. PMID: 24909646. DOI: 10.1111/jdv.12567

9. Ingram JR, et al. Population-based Clinical Practice Research Datalink study using algorithm modelling to identify the true burden of hidradenitis suppurativa. Br J Dermatol. 2018;178(4):917-924. PMID: 29094322. DOI: 10.1111/bjd.16101

10. Saunte DM, et al. Diagnostic delay in hidradenitis suppurativa is a global problem. Br J Dermatol. 2015;173(6):1546-1549. PMID: 26222225. DOI: 10.1111/bjd.14038

11. Jemec GB, et al. The prevalence of hidradenitis suppurativa and its potential precursor lesions. J Am Acad Dermatol. 1996;35(2 Pt 1):191-194. PMID: 8708018. DOI: 10.1016/s0190-9622(96)90321-7

12. Scheinfeld N. Hidradenitis suppurativa in prepubescent children: two case reports and a review of the literature. Pediatr Dermatol. 2014;31(2):203-206. PMID: 24329991. DOI: 10.1111/pde.12276

13. Cosmatos I, et al. Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States. J Am Acad Dermatol. 2013;68(3):412-419. PMID: 23137764. DOI: 10.1016/j.jaad.2012.08.042

14. Garg A, et al. Evaluating patients' unmet needs in hidradenitis suppurativa: results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project. J Am Acad Dermatol. 2020;82(2):366-376. PMID: 31604104. DOI: 10.1016/j.jaad.2019.06.1301

15. Fitzsimmons JS, et al. The genetics of hidradenitis suppurativa. Br J Dermatol. 1985;113(1):1-8. PMID: 4015966. DOI: 10.1111/j.1365-2133.1985.tb02038.x

16. Wang B, et al. Gamma-secretase gene mutations in familial acne inversa. Science. 2010;330(6007):1065. PMID: 20929727. DOI: 10.1126/science.1196284

17. Sartorius K, et al. Comorbidities of hidradenitis suppurativa: a systematic review and meta-analysis. Br J Dermatol. 2018;178(4):964-970. PMID: 29460285. DOI: 10.1111/bjd.16394

18. Miller IM, et al. Association of metabolic syndrome and hidradenitis suppurativa. JAMA Dermatol. 2014;150(12):1273-1280. PMID: 25229996. DOI: 10.1001/jamadermatol.2014.1165

19. Richette P, et al. Hidradenitis suppurativa associated with spondyloarthritis. J Rheumatol. 2014;41(3):490-494. PMID: 24429178. DOI: 10.3899/jrheum.130340

20. Wortsman X, et al. Sonography of hidradenitis suppurativa. J Ultrasound Med. 2013;32(12):2041-2048. PMID: 24277890. DOI: 10.7863/ultra.32.12.2041

21. van der Zee HH, et al. Hidradenitis suppurativa: viewpoint on clinical phenotyping, pathogenesis and novel treatments. Exp Dermatol. 2012;21(10):735-739. PMID: 22882537. DOI: 10.1111/j.1600-0625.2012.01552.x

22. Lima AL, et al. Keratinocyte growth factor and interleukin-36 receptor antagonist deficiency in hidradenitis suppurativa. Br J Dermatol. 2016;174(3):644-653. PMID: 26574236. DOI: 10.1111/bjd.14214

23. Ring HC, et al. The bacteriology of hidradenitis suppurativa: a systematic review. Exp Dermatol. 2015;24(10):727-731. PMID: 26072328. DOI: 10.1111/exd.12793

24. Jahns AC, et al. Microbiology of hidradenitis suppurativa (acne inversa): a histological study of 27 patients. APMIS. 2014;122(9):804-809. PMID: 24460664. DOI: 10.1111/apm.12221

25. Kurek A, et al. Suicide risk in dermatology patients with chronic skin diseases. Int J Dermatol. 2016;55(2):e77-e78. PMID: 26399870. DOI: 10.1111/ijd.13016

26. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach. In: Roenigk RK, Roenigk HH Jr, eds. Dermatologic Surgery. New York, NY: Marcel Dekker; 1989:729-739.

27. Zouboulis CC, et al. Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4). JAMA Dermatol. 2017;153(12):1261-1264. PMID: 29049519. DOI: 10.1001/jamadermatol.2017.3401

28. Wortsman X, et al. Ultrasound for hidradenitis suppurativa in clinical practice. Dermatol Clin. 2019;37(3):385-400. PMID: 31084734. DOI: 10.1016/j.det.2019.03.007

29. Ingram JR, et al. British Association of Dermatologists guidelines for the management of hidradenitis suppurativa (acne inversa) 2018. Br J Dermatol. 2019;180(5):1009-1017. PMID: 30861173. DOI: 10.1111/bjd.17537

30. Zouboulis CC, et al. European S1 guideline on the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29(4):619-644. PMID: 25640693. DOI: 10.1111/jdv.12966

31. Gener G, et al. Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa: a series of 116 consecutive patients. Dermatology. 2009;219(2):148-154. PMID: 19590166. DOI: 10.1159/000228334

32. Nadalin G, et al. Effect of bariatric surgery on hidradenitis suppurativa: a systematic review. Obes Surg. 2019;29(4):1345-1350. PMID: 30666518. DOI: 10.1007/s11695-019-03717-x

33. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol. 1983;22(5):325-328. PMID: 6223874. DOI: 10.1111/j.1365-4362.1983.tb03358.x

34. Verdolini R, et al. Metformin for the treatment of hidradenitis suppurativa: a little help along the way. J Eur Acad Dermatol Venereol. 2013;27(9):1101-1108. PMID: 22882561. DOI: 10.1111/j.1468-3083.2012.04668.x

35. Kimball AB, et al. Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012;157(12):846-855. PMID: 23247938. DOI: 10.7326/0003-4819-157-12-201212180-00004

36. Kimball AB, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375(5):422-434. PMID: 27518661. DOI: 10.1056/NEJMoa1504370

37. Kimball AB, et al. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials. Lancet. 2023;401(10378):747-761. PMID: 36812153. DOI: 10.1016/S0140-6736(23)00022-3

38. Glatt S, et al. Guselkumab for hidradenitis suppurativa: preliminary efficacy and safety findings from a phase 2 trial. J Am Acad Dermatol. 2021;85(1):205-208. PMID: 33385485. DOI: 10.1016/j.jaad.2020.12.078

39. van der Zee HH, et al. Deroofing: a tissue-saving surgical technique for the treatment of mild to moderate hidradenitis suppurativa lesions. J Am Acad Dermatol. 2010;63(3):475-480. PMID: 20646783. DOI: 10.1016/j.jaad.2009.11.679

40. Mehdizadeh A, et al. Surgery for hidradenitis suppurativa. Cochrane Database Syst Rev. 2015;(8):CD011622. PMID: 26258874. DOI: 10.1002/14651858.CD011622.pub2

---

13. Examination Focus

Common Exam Questions

MRCP/MRCS/Dermatology Finals

1. Diagnosis: Q: "What is the pathognomonic sign of hidradenitis suppurativa?"

• Answer: Double comedones (tombstone comedones)—a blackhead with two or more openings from a single dilated follicle.

2. Pathophysiology: Q: "HS is traditionally described as a disease of which glands?"

• Answer: Historically attributed to apocrine glands, but current evidence identifies it as a primary follicular disorder with secondary apocrine involvement.

3. Staging: Q: "How do you differentiate Hurley Stage II from Stage III?"

• Answer:
  • "Stage II: Recurrent abscesses with sinus tracts and scarring, but separated by areas of normal skin"
  • "Stage III: Diffuse or near-diffuse involvement with multiple interconnected tracts; no normal skin between lesions"

4. Treatment: Q: "What is the most effective antibiotic combination for severe HS?"

• Answer: Rifampicin 300 mg BD + Clindamycin 300 mg BD for 10 weeks. 70% response rate in RCT. [31]

Q: "What is the first-line biologic for moderate-to-severe HS?"

• Answer: Adalimumab (Humira) 40 mg weekly. Only FDA/EMA-approved biologic; PIONEER trials demonstrated efficacy. [35,36]

5. Complication: Q: "A 45-year-old man with 20-year history of perineal HS presents with a non-healing, indurated ulcer. What is your concern?"

• Answer: Squamous Cell Carcinoma (SCC) arising in chronic sinus tracts (Marjolin's ulcer). Biopsy urgently.

6. Surgery: Q: "What surgical procedure has the lowest recurrence rate for localized HS?"

• Answer: Wide excision with healing by secondary intention (13% recurrence) vs. local excision (22%) vs. I&D (100%). [40]

---

OSCE/Clinical Examination Scenarios

Station: "Examine this patient's axillae"

Findings:

• Multiple inflammatory nodules (deep, tender, erythematous)
• Draining sinuses (expressing seropurulent discharge on pressure)
• Hypertrophic "rope-like" scarring
• Double comedones (pathognomonic)

Presentation:

• "This patient has hidradenitis suppurativa, a chronic inflammatory disorder of the hair follicle. I can see Hurley Stage II disease with multiple inflammatory nodules, draining sinus tracts, and hypertrophic scarring, but areas of normal skin are still present. The pathognomonic double comedones are visible. I would assess other intertriginous sites (groin, perineum, inframammary) and evaluate for complications such as fistulae or signs of malignant transformation."

---

Viva Voce Points

Examiner: "Why use Rifampicin in HS?"

• Answer:
  • "Mechanism: RNA polymerase inhibitor with excellent biofilm penetration (critical as HS sinus tracts harbor biofilms)"
  • "Anti-inflammatory: Suppresses cytokine production"
  • "Evidence: Clindamycin-Rifampicin combination most effective antibiotic regimen (70% response) [31]"
  • "Important warnings:"
    • CYP450 inducer → renders oral contraceptives ineffective (barrier contraception required)
    • Hepatotoxic → monitor LFTs
    • Drug interactions: Warfarin, antiepileptics, immunosuppressants

Examiner: "Why is HS called a 'follicular' disease now?"

• Answer:
  • Historical view: "Apocrine gland occlusion" (hence "apocrinitis")
  • "Modern evidence: "
    • Monogenic HS (γ-secretase mutations) demonstrates follicular hyperkeratinization as primary defect [16]
    • Histology shows follicular rupture as initiating event
    • Apocrine glands secondarily involved due to anatomical proximity
  • "Clinical implication: Treatments targeting follicular keratinization (retinoids, laser follicle ablation) are rational"

Examiner: "What is the psychological burden of HS?"

• Answer:
  • Highest suicide risk of any dermatological condition [25]
  • DLQI scores worse than psoriasis, eczema [4,5]
  • "Multifactorial causes:"
    • Chronic pain
    • Malodorous discharge → shame, social isolation
    • Sexual dysfunction (genital involvement, pain)
    • Employment difficulties (absenteeism, physical limitations)
  • "Management: Screen for depression (PHQ-9); refer psychology/psychiatry; peer support groups"

Examiner: "When would you consider surgery over medical therapy?"

• Answer:
  • "Indications:"
    • Hurley I/II with localized refractory disease → Deroofing or limited excision
    • Hurley III → Wide excision (most definitive)
    • Failed medical therapy (including biologics)
    • Patient preference (definitive cure for that area)
  • "Advantages: "
    • Wide excision is curative for the excised site (70-90%)
    • Immediate QOL improvement
  • "Limitations:"
    • Does not prevent new sites developing
    • Recurrence if inadequate margins
    • Morbidity (prolonged healing, contracture)

---

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current guidelines.