Hidradenitis Suppurativa Differential Diagnosis: A Comprehensive Guide

Introduction

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil’s disease, is a chronic, debilitating inflammatory skin condition centered around hair follicles. It manifests as painful nodules, abscesses, skin tunnels (sinus tracts), and scarring, primarily in intertriginous areas such as the armpits, groin, perianal, perineal, and inframammary regions. Beyond the physical discomfort, HS significantly impacts patients’ psychosocial well-being due to pain, drainage, odor, and scarring, often leading to delayed diagnosis and a diminished quality of life.

Diagnosing hidradenitis suppurativa is primarily clinical, relying on the recognition of characteristic lesions, their distribution, and chronicity. However, the diagnostic journey is frequently complex and delayed, often because HS can mimic other dermatological and systemic conditions. Accurate diagnosis is paramount as it dictates appropriate management strategies and helps differentiate HS from conditions requiring vastly different treatments. This article provides a comprehensive overview of the Hidradenitis Suppurativa Differential Diagnosis, exploring the key conditions that must be considered to ensure accurate identification and optimal patient care. Understanding the nuances of differential diagnosis in HS is critical for healthcare professionals to improve diagnostic accuracy, reduce delays, and implement effective, tailored treatment plans.

Etiology and Pathophysiology: Key Factors in Differential Diagnosis

While the exact etiology of hidradenitis suppurativa remains incompletely understood, it is recognized as a multifactorial disease involving genetic predisposition, environmental triggers, and behavioral influences. Approximately 30-40% of HS patients report a family history, suggesting a genetic component, with mutations in genes involved in the Notch signaling pathway and others like DCD, PSTPIP1, SOX9, and KLF5 being implicated.

Environmental and lifestyle factors play a significant role in disease development and severity. Obesity, smoking, and hormonal influences are strongly associated with HS. Obesity contributes to increased skin friction, sweat production, and hormonal imbalances, particularly androgen excess, which can exacerbate follicular occlusion. Metabolic syndrome, often linked with obesity, is also more prevalent in HS patients. Smoking has been shown to worsen HS, with nicotine potentially promoting follicular plugging. Hormonal fluctuations, evidenced by the higher prevalence in women, menstrual cycle-related flares, and associations with puberty and menopause, also contribute to HS pathogenesis.

The pathophysiology of HS begins with follicular occlusion, where a defective hair follicle becomes blocked. This occlusion leads to follicular rupture, releasing keratin and bacteria into the dermis, triggering an intense inflammatory response. This response involves the proliferation of keratinocytes and an influx of immune cells, including neutrophils and lymphocytes. The result is the formation of painful abscesses and the destruction of hair follicles, often extending to adjacent tissues, leading to the characteristic skin tunnels and scarring. Abnormalities in antimicrobial peptides, epidermal invaginations, hormonal receptor effects, and complement pathways may also contribute to the disease process. Although bacteria are not considered the primary cause, they can exacerbate inflammation, and secondary bacterial infections are common complications.

Understanding the underlying etiology and pathophysiology is crucial for differential diagnosis. For instance, while bacterial infection is not the primary driver of HS, conditions like folliculitis, furuncles, and carbuncles, which are primarily bacterial infections of the hair follicle, need to be differentiated from early HS lesions. Recognizing the chronic inflammatory nature of HS helps distinguish it from acute infections or cysts.

Clinical Presentation: Mimics and Distinguishing Features

The clinical presentation of hidradenitis suppurativa is characterized by a triad of features: characteristic morphology of lesions (nodules, tunnels, scars), typical location (intertriginous areas), and chronicity (recurrent or persistent course). However, the variability in presentation and overlap with other conditions often leads to diagnostic confusion.

Common HS Lesions:

Nodules: Deep-seated, painful lumps, typically 0.5 to 2 cm in size, which can persist for weeks or months. These are often mistaken for boils or cysts.
Abscesses: Inflamed, pus-filled lesions that can rupture and drain serosanguinous or purulent fluid, often with a foul odor.
Sinus Tracts (Tunnels): Interconnected channels under the skin that drain pus and contribute to chronic drainage and scarring.
Fibrotic Scars: Thick, rope-like scars that develop in areas of recurrent inflammation.
“Tombstone” Comedones: Double-headed blackheads, often seen in HS-affected areas.

Typical Locations:

Axillae (armpits)
Groin and inner thighs
Perianal and perineal areas
Inframammary region (under the breasts)
Buttocks

Prodromal Symptoms:

Many patients experience prodromal symptoms like burning, stinging, itching, warmth, or excessive sweating in the affected areas 12 to 48 hours before lesions appear. Recognizing these symptoms can be helpful in early diagnosis and differentiating HS from acute onset conditions.

Hurley Staging System:

The Hurley staging system is used to classify the severity of HS and aids in treatment decisions but is less directly helpful in differential diagnosis. However, understanding the stage can help differentiate chronic, severe HS from conditions that are typically acute or less progressive.

Hurley Stage I: Isolated abscesses without sinus tracts or scarring.
Hurley Stage II: Recurrent abscesses with sinus tracts and scarring, single or multiple lesions, separated.
Hurley Stage III: Diffuse or broad involvement with multiple interconnected sinus tracts and abscesses across an entire area.

Conditions Mimicking Hidradenitis Suppurativa:

Several conditions can mimic HS, especially in the early stages or in atypical presentations. These include:

Folliculitis, Furuncles, and Carbuncles: These are bacterial infections of hair follicles that can present as painful red bumps or boils. Unlike HS, they are typically acute in onset, often associated with Staphylococcus aureus infection, and resolve with antibiotic treatment. HS lesions are usually recurrent, occur in specific locations, and are not primarily infectious.
Epidermoid, Dermoid, and Pilonidal Cysts: Cysts can present as nodules under the skin, but they lack the inflammatory component and sinus tracts characteristic of HS. Pilonidal cysts occur specifically in the sacrococcygeal region and are related to hair impaction, differing in location and etiology from most HS lesions. Bartholin cysts are located in the vulva and are distinct in location and presentation.
Granuloma Inguinale and Lymphogranuloma Venereum: These sexually transmitted infections can cause lesions in the groin and perineal areas. Granuloma inguinale presents with painless, beefy red ulcers, while lymphogranuloma venereum causes painful inguinal lymphadenopathy and buboes that can ulcerate. Patient history and specific diagnostic tests for STIs are crucial for differentiation.
Noduloulcerative Syphilis: Secondary syphilis can present with skin nodules and ulcers, but it is typically accompanied by systemic symptoms and positive serological tests for syphilis.
Tuberculous Abscess (Scrofula): Cutaneous tuberculosis can cause abscesses, particularly in the axillary or groin regions, but these are often chronic, painless, and may be associated with underlying pulmonary tuberculosis or lymph node involvement. Tuberculin skin test and biopsy with culture are essential for diagnosis.
Actinomycosis: This bacterial infection, often caused by Actinomyces israelii, can form chronic draining sinuses and nodules, but typically occurs in the cervicofacial, abdominal, or pelvic regions. Sulfur granules in the discharge and anaerobic culture help in diagnosis.
Crohn’s Disease (Perianal Involvement): Perianal Crohn’s disease can manifest with fistulas, abscesses, and skin tags around the anus, mimicking perianal HS. However, Crohn’s disease is associated with gastrointestinal symptoms like abdominal pain, diarrhea, and weight loss. Colonoscopy and biopsy can differentiate Crohn’s from HS.
Acne Vulgaris and Acne Conglobata: While HS is sometimes called “acne inversa,” it is distinct from acne vulgaris. Acne vulgaris is characterized by comedones, papules, pustules, and cysts mainly on the face, chest, and back. Acne conglobata is a severe form of acne with interconnecting abscesses and nodules, but it typically occurs on the back, chest, and face, not primarily in intertriginous areas like HS. However, acne conglobata is part of the follicular occlusion tetrad along with HS, dissecting cellulitis of the scalp, and pilonidal sinus, and co-occurrence should be considered.
Dissecting Cellulitis of the Scalp: This condition presents with painful nodules, abscesses, and draining sinuses on the scalp, potentially mimicking HS in less common scalp involvement. However, the location is distinct, and scalp cellulitis often leads to scarring alopecia.
Pyoderma Gangrenosum: This inflammatory skin condition causes painful ulcers that can resemble ruptured HS abscesses. However, pyoderma gangrenosum ulcers typically have undermined, violaceous borders and can occur anywhere on the body, often associated with systemic inflammatory diseases like inflammatory bowel disease.

Diagnostic Evaluation: Ruling Out Mimicking Conditions

Hidradenitis suppurativa diagnosis is primarily clinical, based on history and physical examination. However, in cases where the presentation is atypical or differential diagnoses are strongly considered, further evaluation may be necessary to exclude other conditions.

Key Diagnostic Steps:

Detailed History: Gather information about the onset, duration, location, and characteristics of lesions, triggers (menstruation, stress, weight gain, smoking), family history of HS or similar conditions, and relevant past medical history (inflammatory bowel disease, metabolic syndrome, etc.).
Thorough Physical Examination: Assess the morphology, distribution, and stage of lesions. Palpate for sinus tracts and scarring. Document the location and extent of involvement.
Skin Biopsy: While not routinely required for HS diagnosis, a skin biopsy can be helpful in uncertain cases to rule out other conditions, especially squamous cell carcinoma in long-standing lesions. Histopathological features of HS include follicular occlusion, hyperkeratosis, perifolliculitis, and pseudoepitheliomatous hyperplasia. Biopsy can help differentiate HS from granulomatous diseases (Crohn’s, sarcoidosis, mycobacterial infections), chronic deep folliculitis, Langerhans cell histiocytosis, and folliculotropic mycosis fungoides.
Bacterial Cultures: Routine bacterial cultures are generally not helpful as HS lesions are not primarily infectious. However, cultures may be considered if secondary infection is suspected or to rule out bacterial infections like furuncles or carbuncles. Aspirates from unruptured HS lesions are often sterile.
Imaging: Imaging is not typically used for HS diagnosis, but ultrasonography can be helpful to visualize skin tunnels preoperatively or to assess the extent of disease. In severe perianal disease, MRI may be warranted to evaluate for complex fistulizing disease, especially to differentiate from perianal Crohn’s disease.
Laboratory Tests: There are no specific lab tests to diagnose HS. However, baseline labs may be ordered to assess for associated comorbidities like metabolic syndrome, dyslipidemia, and diabetes. In differential diagnosis, specific tests may be required to rule out other conditions (e.g., serology for syphilis, tuberculin skin test for tuberculosis, stool studies and endoscopy for Crohn’s disease).

Differential Diagnosis-Focused Evaluation:

When considering the hidradenitis suppurativa differential diagnosis, specific evaluations may be indicated based on clinical suspicion:

Suspected Infection (Folliculitis, Carbuncles, Actinomycosis, Tuberculosis): Bacterial culture and sensitivity, Gram stain, fungal stain, acid-fast stain, tuberculin skin test (TST) or Interferon-Gamma Release Assay (IGRA), chest X-ray (for tuberculosis), biopsy for histopathology and culture.
Suspected Sexually Transmitted Infections (Granuloma Inguinale, Lymphogranuloma Venereum, Syphilis): Darkfield microscopy (for syphilis), serological tests for syphilis (VDRL, RPR, FTA-ABS), PCR or culture for Klebsiella granulomatis (granuloma inguinale), serology or PCR for Chlamydia trachomatis (lymphogranuloma venereum).
Suspected Cystic Lesions (Epidermoid, Dermoid, Pilonidal, Bartholin Cysts): Clinical examination usually suffices. Ultrasound may help differentiate complex cysts or rule out abscess formation.
Suspected Inflammatory Bowel Disease (Crohn’s Disease): Colonoscopy with biopsy, stool studies (fecal calprotectin, stool culture), imaging (CT or MRI enterography).
Suspected Pyoderma Gangrenosum: Clinical correlation with history of inflammatory bowel disease or other systemic conditions. Biopsy may be non-specific but helps rule out infection. Pathergy test (controversial and not routinely recommended).

Treatment and Management: Impact of Differential Diagnosis

Accurate differential diagnosis is not only crucial for identifying hidradenitis suppurativa but also for guiding appropriate treatment. Misdiagnosis can lead to ineffective or even harmful treatments. For instance, misdiagnosing HS as a simple bacterial infection and treating solely with antibiotics may provide temporary relief but will not address the chronic inflammatory nature of HS and can contribute to antibiotic resistance. Conversely, treating a bacterial infection with immunosuppressive therapies appropriate for HS would be detrimental.

Treatment Strategies Based on Accurate Diagnosis:

Hidradenitis Suppurativa: Treatment is multimodal and depends on disease severity (Hurley stage) and patient-specific factors. It includes lifestyle modifications (weight loss, smoking cessation, loose clothing), topical treatments (clindamycin, resorcinol), systemic antibiotics (tetracyclines, clindamycin with rifampin), anti-inflammatory agents (adalimumab, infliximab, secukinumab), hormone therapy (spironolactone, oral contraceptives), pain management, and surgical interventions (deroofing, excision).
Bacterial Infections (Folliculitis, Furuncles, Carbuncles, Actinomycosis, Tuberculosis): Antibiotics are the mainstay of treatment. Topical antibiotics (mupirocin, clindamycin) for mild folliculitis and furuncles. Oral antibiotics (dicloxacillin, cephalexin, clindamycin) for more extensive infections or carbuncles. Prolonged antibiotics (penicillin, tetracycline) for actinomycosis. Multi-drug therapy (isoniazid, rifampin, ethambutol, pyrazinamide) for tuberculous abscesses. Drainage of abscesses may be necessary.
Sexually Transmitted Infections (Granuloma Inguinale, Lymphogranuloma Venereum, Syphilis): Antibiotics specific to the causative organism. Azithromycin or doxycycline for granuloma inguinale. Doxycycline for lymphogranuloma venereum. Penicillin for syphilis.
Cysts (Epidermoid, Dermoid, Pilonidal, Bartholin Cysts): Often require surgical excision or incision and drainage if symptomatic or infected. Antibiotics are used for secondary infections.
Crohn’s Disease (Perianal Involvement): Management involves treatment of underlying Crohn’s disease with medications like aminosalicylates, corticosteroids, immunomodulators (azathioprine, methotrexate), and biologics (infliximab, adalimumab, ustekinumab). Surgical management of perianal fistulas and abscesses may be necessary.
Pyoderma Gangrenosum: Topical and systemic corticosteroids, cyclosporine, tacrolimus, biologics (infliximab, adalimumab, ustekinumab). Wound care and pain management are crucial. Avoidance of surgical debridement as it can worsen lesions (pathergy).

Prognosis and Complications: The Role of Early and Accurate Diagnosis

The prognosis of hidradenitis suppurativa is variable. It is a chronic condition with a relapsing and remitting course. However, early and accurate diagnosis is crucial for improving the long-term prognosis and preventing complications. Delayed diagnosis and treatment are associated with more severe disease progression, increased scarring, and a higher risk of complications.

Complications of Hidradenitis Suppurativa:

Physical Complications: Chronic pain, contractures, limited mobility, lymphedema, anemia, amyloidosis, arthropathy, secondary bacterial infections, squamous cell carcinoma (rare but serious, especially in chronic draining lesions), increased risk of certain cancers (buccal and hepatocellular).
Psychosocial Complications: Depression, anxiety, social isolation, sexual dysfunction, reduced quality of life, employment difficulties, suicidality.

Impact of Differential Diagnosis on Prognosis:

Early Diagnosis and Treatment: Accurate differential diagnosis allows for prompt initiation of appropriate HS-specific treatment, which can help control symptoms, reduce the frequency and severity of flares, and prevent disease progression and complications.
Avoiding Inappropriate Treatments: Correct diagnosis prevents the use of ineffective or harmful treatments, such as prolonged courses of antibiotics alone for HS or immunosuppressants for bacterial infections, which can worsen the patient’s condition and delay effective management.
Comorbidity Management: Recognizing HS also prompts evaluation for and management of associated comorbidities like metabolic syndrome, cardiovascular disease, and mental health conditions, improving overall patient health and prognosis.

Conclusion

The hidradenitis suppurativa differential diagnosis is a critical aspect of patient care. HS can mimic a range of dermatological and systemic conditions, leading to diagnostic delays and inappropriate management. A thorough understanding of HS clinical presentation, etiology, and pathophysiology, combined with a systematic approach to evaluation and differential diagnosis, is essential for healthcare professionals. By carefully considering conditions like bacterial infections, cysts, sexually transmitted infections, inflammatory bowel disease, and other inflammatory dermatoses, clinicians can improve diagnostic accuracy, initiate timely and effective treatment, and ultimately enhance the quality of life for individuals living with hidradenitis suppurativa. Interprofessional collaboration, involving dermatologists, primary care physicians, surgeons, nurses, and pharmacists, is crucial for comprehensive management and addressing the multifaceted needs of HS patients. Early and accurate diagnosis, guided by a robust understanding of differential diagnosis, remains the cornerstone of effective HS care and improved patient outcomes.

Image: Hidradenitis Suppurativa in the left axilla, showing multiple nodules and fibrotic scars, highlighting the characteristic lesions in a common location for differential diagnosis from other axillary conditions.

Image: Hidradenitis Suppurativa in the groin area, demonstrating nodules and scarring, typical presentations that require differential diagnosis from inguinal and genital conditions.

Image: Hidradenitis Suppurativa in the suprapubic region, showing nodules and scarring, indicating the varied locations where HS can occur and necessitate differential diagnosis from other skin conditions.

References

[References from the original article – same as provided]

Disclosure: Kimberly Ballard declares no relevant financial relationships with ineligible companies.

Disclosure: Victoria Shuman declares no relevant financial relationships with ineligible companies.