HIDRADENITIS SUPPURATIVA

Definition – Hidradenitis suppurativa is a chronic follicular occlusive disease, characterized by recurrent painful, deep-seated nodules and abscesses located primarily in the axillae, groins, perianal, perineal and inframammary regions. In milder cases it is an inflammatory folliculopustular disease; in severe cases hypertrophic scarring, sinus and fistula formation occur. It has a profound impact on the quality of life.

1. The prevalence of hidradenitis suppurativa (HS) is described as anywhere from 1 in one hundred to 1 in six hundred. Women are more commonly affected than men. Some studies have described a predilection in patients of afro-carib descent, but this has not been confirmed in all. 25% of patients present between the ages of 15 and 20 and 53% are aged 21 to 30. Female to male ratios range from 2:1 to 5:1. Prepubertal cases are rare, but occasional onset in neonates and infants has been described. . It is felt to arise secondary to some defect in the terminal follicular epithelium. The initial process is cornification of the follicular infundibulum followed by follicular occlusion. Folliculitis and destruction of the skin appendages and subcutaneous tissue occur. As the disease progresses, abscess and sinus tract formation occur. Apocrine glands become involved in the context of intense peri-follicular inflammation. Most recent papers concur that bacterial involvement is secondary and not causative to the disease process. The exact etiology of hidradenitis is unknown.

Diagnosis-Relies on three main features:
Typical lesions. i.e. deep-seated nodules ( blind boils ) and/or fibrosis
Typical localization to axillae and groins
Patterns of relapses and chronicity
Multiple skin abscesses occur, with draining subcutaneous sinus tracts. Scarring and deformity are present in many individuals. Although biopsy is not absolutely required for diagnosis of HS, if you send tissue to pathology and tell them that the clinical picture is consistent with HS, they will likely look for the characteristic findings of follicular hyperkeratosis, active folliculitis or abscess, sinus tract formation, fibrosis, granuloma formation, apocrine and eccrine stasis and inflammation, fibrosis, fat necrosis, inflammation of the subcutis.
Differential diagnosis –Multiple conditions are to be considered in the differential diagnosis of hidradenitis suppurativa. These include acne vulgaris, carbuncles and furuncles, infected Bartholin’s duct cysts, infected or non-inflamed epidermoid cysts, granuloma inguinale, lymphogranuloma venerum, deep mycoses, developmental fistulae, and Crohn disease.
TREATMENT PRINCIPLES
Therapy and prognosis – Planning treatment follows severity grading. The first two stages respond to medical treatment whereas the third stage requires biologics and surgery. All patients will need thorough education and constant reassurance and support.
Treatment
– Define the frequency of the flares and the intensity of the pain when deciding upon treatment.
– A permanent cure is achieved only with wide , thorough, surgical excision
– Combine medical and surgical treatment
Goals of treatment of hidradenitis:
1. To reduce the extent and progression of the disease to bring it to a milder stage
2. To heal existing lesions and prevent new ones from forming
3. To allow regression of scars and sinuses in cases of extensive hidradenitis suppurativa
Hurley’s criteria for Hidradenitis Suppurativa Staging
Hurley’s criteria for Hidradenitis Suppurativa Staging – used to assess severity
Treatment principles – choose treatment to fit disease severity staging
Stage I: Abscess formation, single or multiple without sinus tracts
and cicatrisation/scarring.
Stage II: Recurrent abscesses with sinus tracts and scarring.
Single or multiple widely separated lesions
Stage III: Diffuse or almost diffuse involvement or multiple interconnected
tracts and abscess
75% stay in Stage I
24% progress to Stage II
1% progress to Stage III
General Hidradenitis Suppurativa Treatment
Education and support
Improve environment:
Reduce friction in the area, heat, sweating and obesity
Use antiseptic washes
Consider anti-androgen treatment
Stop smoking
Treatment – Hurley’s Stage I
Abscess formation, single or multiple without sinus tracts and cicatrisation/scarring.
This is the most limited form of disease and it is amenable to medical therapy.
The majority of patients with Stage I have a few flares a year, however they can be well controlled.
Medical Treatment for Stage 1 hidradenitis suppurativa
Topical antibiotics
Clindamycin 1% lotion bid
Intralesional
Triamcinolone acetonide 10 mg/mL, 0.5 to 1 ml injected with a 30g needle into individual, painful, early papules / small nodules to suppress inflammation. Inject right into the center of the lesion
Systemic Antibiotics (for 7-10 days) – wide choice
Tetracycline 250-500mg po qid or doxycycline 100 mg po bid or clindamycin 300 mg po bid, or amoxicillin/ clavulanic acid 500mg-1gm po q 8h
Caution in patients with diabetes- high dose steroids can interfere with their glucose control.
Adjunct preventive therapy
Zinc gluconate 50 mg po bid
Anti-androgens
Yasmin – consider extended regimen (daily x 84 – 126 days)
Yasmin plus spironolactone
Surgical Treatment – not usually needed for Hurley’s Stage I
General Care
Avoid irritants
Loose clothing
Stop smoking
Weight loss
Maintenance
Continue above as needed
Treatment – Hurley’s Stage II
Recurrent abscesses with sinus tract formation and scarring, either single or multiple widely separated lesions
The aim is to clear these patients or at least reduce them to stage I disease.
If there are sinus tracts and scarring this will require combined medical and surgical therapy. For those with little scarring and much inflammation use antibiotics such as rifampin and /or clindamycin for 3 months and then decrease to maintenance on tetracyclines and/or high dose zinc and/or dapsone.
General care and intralesional treatment is the same as for stage I. Antibiotics for at least three months are usual, with a decreased dose for maintenance. Systemic antibiotics include tetracycline, as above or, for more extensive disease, clindamycin 300 mg twice a day often combined with rifampin 300 mg twice a day for three months. ( See below for prescribing details ) Dapsone 100 mg per day can be used. ( See below for prescribing details ) Long-term maintenance is with a tetracycline etc. (as below) is often recommended. The same adjunctive therapy with zinc gluconate and anti-androgens can be used as above.
A. Medical Treatment for Stage II
Topical antibiotics
Clindamycin 1% lotion twice a day
Systemic Antibiotics
Amoxicillin and clavulanic acid 3g loading then 1g po q8h for 5-7 days for acute painful lesions or
Clindamycin 300 mg po bid with / without Rifampin 300 mg po bid or Dapsone 50 mg po and then 100 mg po with the appropriate blood work ( See below for prescribing details).
Maintenance – Tetracycline 250-500 mg qid, doxycycline or minocycline 100 mg bid
Adjunct preventive therapy
Zinc gluconate 50 mg po bid
Anti-androgens
Yasmin – consider extended regimen (daily x 84 – 126 days)
Yasmin plus spironolactone
Intralesional triamcinolone as in Stage I
B. Surgical Treatment –Incision and drainage (I and D) should be avoided. Only do this for a tense abscess that is too painful to bear. Acute painful lesions sometimes develop into severely painful abscesses that need to be drained for pain relief only. This is not a curative procedure and needs concurrent antibiotics in full dose. Amoxicillin and clavulanic acid 3g in a single dose, then one gram po tid for 5-7 days is recommended. The lesion must be incised. Packing the wound for a few days may be needed to prevent premature superficial closure while the wound fills in from below. If there are persistent chronic sinus tracts or cysts then obsessive surgical unroofing is necessary
C. and D. General Care and Maintenance- as for Stage I
Treatment – Hurley’s Stage III
Diffuse or almost diffuse involvement or multiple interconnected
tracts and abscess
This stage is a surgical disease and supportive concurrent medical treatment is both prophylactic and essential. This requires a staged medical – surgical team approach
A. Medical Treatment
.Pre-Op -These patients will need the anti-inflammatory effects of medical treatment to prepare them for surgical treatment.
Corticosteroids 0.5 – 0.7 mg/kg/d methylprednisolone or prednisone (oral)
Cyclosporine 4 mg/kg/d po
Methotrexate 15 mg oral or subcutaneously weekly
TNF-α inhibitors
Remicade 5 mg/kg I.V Q6 weeks – use with the help of a knowledgeable health care provider
Clindamycin 300 mg po bid with Rifampicin 300 mg po bid
Note – Medical treatment at this stage is only palliative and temporary.
B. Surgical Treatment
Wide surgical unroofing and debriding of all cysts and sinuses and fistulous tissue by a knowledgeable surgeon. Healing can be by secondary intent or it may be accelerated with mesh grafting. Primary closure is avoided in active disease. At times skin flaps are required.
A bowel preparation prior to surgery is important if the anal area is involved and a wound VAC over that area is anticipated. The patients should be evaluated for malnutrition prior to surgery.
Pre-operative Clinic: Reminders for Hidradenitis Patients
1. Consider Nutrition consult- screening tool per nutrition: albumin and prealbumin with preop labs
2. Encourage tobacco cessation; discuss impact on wound healing, need for avoidance of nicotine replacement products post-operatively.
3. Give instructions for Fleets Phospho-soda bowel prep, use Golytely prep if h/o kidney or heart disease.
4. Consider Aranesp (darbopoetin) 40 mcg SQ weekly if Hgb <12 gm/dl, must use with FeSO4 supplementation (325 mg PO daily.)
5. If not on oral contraceptives, try to schedule surgery in luteal phase to avoid menses in post-operative time frame.
6. Counsel regarding the extent of excision, possibility of recurrence, prolonged hospitalization (at bed rest) and healing time.
Intra-operative: Have Available in OR
2. VAC machine, canister and dressings The VAC helps to promote granulation tissue formation by aiding in the wound healing process, Applies localized negative pressure
to help uniformly draw wounds closed, Helps remove interstitial fluid and infectious material, Provides a closed, moist wound healing environment, It promotes flap and graft survival.
1. Cavilon barrier film skin prep to put under flexiseal and VAC
2. Black (granu foam) for post-vulvectomy, White (Vers foam) for post-skin graft
3. Adaptic sheets to place over wound bed prior to placing VAC foam
4. Supplies for aerobic and anaerobic culture of wound bed
5. Flexi-seal bowel system
6. Consider epidural
7. For skin grafting procedure, have available large curette used by plastic surgery for debridement.
Post-Op – They will need ongoing medical treatment after surgery. Postoperative medical management to prevent recurrence or minimize recurrence is recommended.
These patients require a lot of support and help with pain management.
any persistent sinuses, wide local unroofing surgery is necessary .
Post-operative Considerations
1. Check wound cultures, check if bacteria resistant to present antibiotic, or if sterile culture, consider discontinuing antibiotics.
2. If perianal area involved and resected, start hyperal following surgery
3. If wound VAC covers anal area, keep NPO so that stool does not leak into wound VAC
4. Nestle Fruit Beverage (clear liquid supplement)
(See http://www.med.umich.edu/obgyn/resdir/protocols/Hidradenitis/index.htm for information on bowel prep, surgical orders and nutrition status).
Prognosis – The majority of patients are in stage 1 and can be controlled well. Stage 2 can be more difficult and Stage 3 is very difficult and requires a multi-disciplinary treatment approach. Average duration of disease is 20 years. Squamous cell carcinoma may occur in patients with HS. It tends to be seen in patients who have suffered from HS for ten years or more, will often be advanced in stage at diagnosis.
Specific Drug Information for Medications Used in the Treatment of Hidradenitis Suppurativa
CLINDAMYCIN
In hidradenitis, clindamycin is used as an anti-inflammatory medication.
– helps settle down the redness, swelling, etc.
It is also a very effective medication for bacterial infections.
Side effects
Bowel inflammation can occur due to an overgrowth in the bowel of bacteria (C. difficile) that release a toxin. This can occur in a few patients. If there is any problem with diarrhea, stop the medication. Other side effects include upset stomach, vomiting, and skin rashes. Clindamycin can be taken with the rifampin or used separately.
Dose – 150 – 300 mg po twice a day – to be taken with food. Use for 3-6 months.
Interactions – can interact with birth control pills
AMOXICILLIN / CLAVULANATE
Used as an anti-inflammatory
Dose – For acute nodules and incised abscessed lesions – amoxicillin and clavulanic acid 3g loading then 1g po q 8h for 5-7 days (taken with food). For indolent nodules, 500 mg po tid for 1-2 weeks.
Side effects – allergy, GI upset, nausea, diarrhea, yeast, rashes
Contraindications – hypersensitivity
Indications – For acute nodular flares.
ZINC GLUCONATE
Zinc gluconate is anti-inflammatory and helps in wound healing.
Dose is 50 -mg po bid ; it is suppressive rather than curative
Side effects are occasional GI upset with nausea and / or diarrhea.
Zinc in high doses can affect iron in the body with resulting anemia and drop in white count.
Do not increase the dose of zinc.
RIFAMPIN
Rifampin 150 and 300 mg tablets – this is an antibacterial agent that is used for bacterial infections, both common ones and mycobacteria including tuberculosis. This medication is used in hidradenitis suppurativa as an anti-inflammatory and is usually combined with other medications.
Dose – 150 – 300 mg po twice a day. Take on an empty stomach. It is occasionally given as 600 mg in one dose. It can be given with other medication such as clindamycin taken in two doses daily or may be given as a single dose with a large glass of water at 4 AM to prevent any interaction with the other medicines.
Monitoring blood tests for Rifampin – baseline CBC, renal and liver function tests should be taken. Caution should be taken if there is pre-existing liver disease or liver function abnormalities. Repeat blood tests at 2-4 week intervals as needed.
Drug interactions – many may occur
Birth control pills – decreases effect of BCP
Blood thinning drugs – increases INR / clotting time
Heart drugs – digoxin, quinidine
Beta blockers – verapamil
Anti-convulsants –phenobarbital, phenytoin
Anti-fungal drugs – ketoconazole
Bronchodilators – theophylline
Immunosuppressant drugs – cyclosporine
Corticosteroids
Sulfonylurea and other hypoglycemic medications
Miscellaneous – acetaminophen, dapsone.
Enalapril can result in an increase in blood pressure.
Side effects
Urine discoloration – orange red
Permanent staining of soft contact lenses
Allergic reactions
Flu-like syndrome with fever, chills, headache, dizziness & rashes
Skin rashes – itching, hives, pimply reactions, and blisters, rarely erythema multiforme or toxic epidermal necrolysis
Dizziness, headache and fatigue can occur
Rarely anemia and hepatitis
DAPSONE
This is used as an anti-inflammatory. It reduces PMN/WBCs in tissue
Dose – 50 – 100 mg po per day. Start at 50 mg/day for first 2-4 weeks
Caution – the glucose-6 phosphate dehydrogenase should be measured. If this is low there is a higher risk of blood problems such as anemia.
This can be more of a problem for some African Americans and Asians resulting in a more toxic reaction from the dapsone. Dapsone affects red blood cells so that they do not “live as long”. Usually red blood cells last for 120 days but when a patient is on dapsone this can decrease to 80 days causing the hemoglobin, to drop. This can be a problem in patients with heart, liver and kidney disease. A thorough history and physical with attention to the heart, liver and renal function is important.
Patients must be checked to be sure there is no anemia.
Contraindications to the use of dapsone include prior hypersensitivity and agranulocytosis. Paztient with severe allergy (hypersensitivity) to sulfonamides may be allergic to dapsone. If a mild allergy to sulfonamides, this is less likely.
Relative contraindication would be significant cardiopulmonary disease, G-6PD deficiency, and severe sulfonamide allergy.
Monitoring blood tests for patients for dapsone
1. G-6PD level must be assessed.
2. CBC with differential, liver function tests, BUN, creatinine and urinalysis.
3. Repeat blood work – CBC with differential, WBC and reticulocyte count every week for 4 weeks and then every 2 weeks for 8 weeks and then about every 3-4 months. Check reticulocyte count to assess response to Dapsone hemolysis.
4. Liver function and renal function tests every 4 months for maintenance.
Drug interactions
1. Dapsone levels are increased with trimethoprim, probenecid
2. Dapsone levels decreased with rifampin
3. Dapsone, if combined with hydroxychloroquine and sulfonamides, yields more red blood cell toxicity
Cross Reactions
Other sulfonamide type drugs – patients with severe allergic reactions to sulfonamide medications may be allergic to Dapsone. This is very rare.
Adverse Effects
1. Hemolytic anemia, methemoglobinemia – symptoms headache, lethargy
2. Hepatotoxicity – mono-like syndrome
3. Peripheral neuropathy
4. Allergy – rashes etc.
5. GI upset
http://www.hs-foundation.org/