Clostridium difficile arising in a patient with hidradenitis suppurativa on clindamycin and rifampin.

We report a case of Clostridium difficile infection in a patient with hidradenitis suppurativa who was taking clindamycin and rifampin. Clostridium difficile infection treatment prompted discontinuation of the medication. Clostridium difficile infection is known to develop after antibiotic treatment, such as clindamycin, but has rarely been associated with anti-tuberculosis agents, such as rifampin. Clinicians should be aware of the risk of Clostridium difficile infection in patients with hidradenitis suppurativa, even in those receiving rifampin.

Squamous cell carcinoma of the cervix arising in a patient on adalimumab � a need for cervical screenings in patients on tumor necrosis factor inhibitors.

Adalimumab, a tumor necrosis factor (TNF) inhibitor, has been approved for treatment of hidradenitis suppurativa. We report a case of cervical cancer in a patient with hidradenitis suppurativa taking adalimumab, which prompted discontinuation of the medication. Physicians should obtain a detailed cervical medical history before putting a female patient on a TNF inhibitor. Patients on TNF inhibitors who have pre-existing cervical issues such as human papillomavirus (HPV), dysplasia, or high grade intraepithelial lesions should be counseled about an increased risk of developing squamous cell carcinoma (SCC) of the cervix while on a TNF inhibitor. Furthermore, patients on TNF inhibitors should comply with the national screening guidelines for cervical cancer and be tested for human papillomavirus.

Why rifampin (rifampicin) is a key component in the antibiotic treatment of hidradenitis suppurativa: a review of rifampin's effects on bacteria, bacterial biofilms, and the human immune system.

Combinations of rifampin and clindamycin or rifampin, metronidazole, and moxifloxcin have been reported as effective treatments for hidradenitis suppurativa (HS) Hurley Stage 1 and Hurley Stage 2.  Clinical trials suggest that for stage 1 and mild stage 2 HS, clindamycin 300 mg twice daily and rifampin 300 mg twice daily for 10 weeks can substantially abate HS in ~80% of cases and remit HS in ~50% of cases.  Another study notes use of rifampin-moxifloxacin-metronidazole given for 6 weeks, dosed as rifampin (10 mg/kg once daily), moxifloxacin (400 mg daily), and metronidazole (500 mg thrice daily) with the metronidazole stopped at week 6.   Rifampin and moxifloxacin were continued if the HS improved and side effects did not occur.  Using this triple antibiotic regimen remission occurred in 100% Hurley Stage 1, 80% Hurly Stage 2, and 16.7 % of Hurley Stage 3 HS.   The author typically gives HS clindamycin 300 mg and rifampin 300 mg, each twice daily, for 10 weeks and assesses if remission has occurred.  If the patient has not achieved remission the author continues the regimen as long as the patient's clinical status continues to improve without side effects.  The reasons why rifampin is so effective against HS have not been fully defined and might involve rifampin's (1) antibacterial effects (2) effects on bacterial biofilms (3) anti-inflammatory effects (4) effects against granulomas (5) and immunomodulatory effects on neutrophils.  It is notable that rifampin, although not first line, is an effective treatment for Clostridium difficile, a pathogen that arises during treatment with clindamycin.  Thus, rifampin enhances safety when rifampin and clindamycin are combined for the treatment of HS.

Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease with frequent comorbidities of painand depression. Adalimumab treatment for 16 weeks improved HS lesions significantly versus placebo (NCT00918255). OBJECTIVE: The relationship between pain and depressive symptoms and the effects of adalimumab on each was examined in this post hoc analysis. METHODS: Patients with moderate to severe HS (N=154) were randomized 1:1:1 to adalimumab 40 mg weekly (ew), adalimumab 40 mg every other week (eow), or placebo. Skin pain was assessed using a visual analog scale (VAS; 0-100 mm). Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9; score ≥10 indicative of depression). RESULTS: At baseline, overall mean±SD pain VAS was 54.3±26.5 mm and 41.8% of patients had PHQ-9 scores ≥10. At baseline, VAS pain scores (mean±SD) were significantly higher (P<0.001) for patients with PHQ-9 scores ≥10 (63.9±23.3) versus <10 (47.4±26.7). At Week 16, clinically relevant pain reduction was observed for ew-treated patients with baseline PHQ-9 score ≥10 (ew, 45.8%; eow, 29.4%; placebo, 23.8%) and <10 (ew, 50.0%; eow, 37.9%; placebo, 29.6%), but did not reach statistical significance. In patients with high baseline pain (≥median VAS score), adalimumab ew significantly decreased depressivesymptoms versus placebo (PHQ-9 scores, -34.03% vs +2.26%; P<0.01). CONCLUSION: Patients with moderate to severe HS had a high degree of pain and depressive symptoms at baseline. Adalimumabtherapy was associated with decreased pain and depressive symptoms compared to baseline.

Topical AC-11 abates actinic keratoses and early squamous cell cancers in hairless mice exposed to Ultraviolet A (UVA) radiation.

AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (< 0.05%, w/w) but contains more than 8% carboxy alkyl esters (CAEs) as their active ingredients. Three groups of 10 outbred SK-1 hairless or SK-II hairless strains of mice each were treated with AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishing cream vehicle. Ten mice used vehicle only and 10 were untreated. Each concentration of AC-11 and was applied daily to the backs of the mice prior to exposure to a 1,600-watt solar simulator used in this work (Solar Light Co. Philadelphia, PA) emitting (mainly Ultraviolet A (UVA) and B (UVB) radiation) duration of the experimental period with UVB wavelengths was filtered out with a 1.0 cm Schott WG 345 filter. AC-11 with a peak absorption at 200nm does act as a sun block. We tested for and focused on clinical appearance of mice and histological appearance of tumors in mice rather than metrics of radiation generated inflammation. Tumor progression scores were assigned as follows: 4+ = extensive tumor development; 3+ = early malignancies (raised palpable plaques)(early squamous cell cancers) 2+ = firm scaling, palpable keratosis (actinic keratoses); 1+ = light scaling with erythema. Following a total cumulative dose of 738 J/cm2, 85.7% all of the irradiated control animals, which did not receive AC-11 had precancerous actinic keratosis (AK)-type lesions (2+) (64.3% versus 42.9%) or early squamous cell carcinoma (SCC) (3+) (21.4% vs. 4.8%), in comparison with 47.7 % of AC-11-treated animals. There were no significant differences between the AC-11 groups. Three months after cessation of exposure to UVA radiation, the lesions in all but three of the 14 animals which were treated with AC-11 that were still evaluable irradiated with UVA radiation progressed to papillomas and frank squamous cell carcinomas (+4 responses). AC-11 retarded, but did not stop, carcinogenesis progression. It is possible that if AC-11 was continuously applied tumors would not have in mice treated with AC-11 for a limited period. While we do not know how AC-11 exerts its DNA repair and anti-inflammatory effects, AC-11 is therapeutic for the treatment at the time of development of actinic keratoses and squamous cell carcinomas in mice and by extension humans. Without the constant presence of AC-11 these protective effects do not occur.

Hidradenitis Suppurativa in prepubescent and pubescent children.

Hidradenitis Suppurativa (HS) is an uncommon disease, which is particularly rare in young and prepubescent children. HS pathology centers on the follicular unit and involves aberrant cutaneous cellular immunity. HS tends to first manifest in puberty, but a handful of prepubescent cases of HS have been reported and are linked to hormonal disorders, in particular elevated testosterone. The most common manifestations of HS are abscesses, scarring, acne inversa, and keloids, especially in the intertriginous areas of the groin and the axilla. Treatments including topical anti-infectives including chlorhexidine wash, topical clindamycin, tretinoin cream, and azelaic acid cream, which may be of limited use because bacteria involved in HS likely create biofilms. Oral agents include clindamycin with or without rifampin for short-term usage. Cases resistant to conservative therapy have been reported to respond to finasteride, onabotulinumtoxin, or microfractionated 10,600-nm CO2 laser.

Extensive hidradenitis suppurativa (HS) Hurly stage III disease treated with intravenous (IV) linezolid and meropenem with rapid remission.

A 57-year-old woman with Hurley Stage 3 hidradenitis suppurativa (HS) and multiple co-morbidities is presented. She had failed multiple antibiotic therapies and etanercept. She had end stage renal disease and was on dialysis. Her HS was put into remission with one month of daily IV treatment with 1.2 grams linezolid and 1 gram of meropenem, administered daily through her dialysis shunt. Unfortunately, her disease flared again two weeks after the cessation of the IV treatment. Nevertheless, more conventional therapy was then able to maintain her disease at a level that was significantly improved over baseline prior to the IV treatment. This case highlights above all a primary etiology of HS is stimulus of immune system's over-reaction in HS to the bacterial microbiome. If antibiotics are administered to a patient with stage 3 HS powerful enough to wipe out the bacterial biome, the immune system having no target retreats, permanent scarring in its wake and retreats to a certain but hardly permanent normalcy.

The use of photodynamic therapy to treat hidradenitis suppurativa a review and critical analysis.

Hidradenitis Suppurativa (HS) is an inflammatory disease that results in abscesses, keloids, and fistulas. Acne inversa is likely to result from aberrant cellular immunity and dysfunction of the hair follicle in which coagulase negative staphylococcus (CONS) and perhaps other bacteria appear e.g Corynebacterium sp.to play a role by creating biofilms and stimulating the immune system. One treatment that has been proposed for HS is photodynamic therapy. The cases series reported are small and not double blinded. As of October of 2104, 8 articles with 64 patients report success with photodynamic therapy using 5-aminolevulinic acid (PDT-ALA) or its methyl ester (PDT-MAL). One of these 8 reports noted superiority of the free methylene blue gel over niosomal methylene blue gel. Another report described success in a 27-patient trial using intralesional 5-aminolevulinic acid (ALA) in saline at a concentration of 1%. This was administered at a dose of 0.2 ml per cm3 and an HS fistula was irradiated by a continuous 630-nm laser diode through a 1-mm thick optical fiber to 1 Watt per cm3 for 3 minutes (180 Joules). However, 3 articles reported failure with PDT-ALA or pulse dye laser-mediated photodynamic therapy (PDL-PDT) and one article note 1 failure and 1 success. We suggest that it is the ability of PDT-ALA or PDT-MAL to break up the bio-film produced by CONS and other antibacterial effects that account for its success in treating HS in patients in whom bio-film plays a pivotal part of their pathogenesis. Other effects are also possible as well. Other mechanisms by which PDT may improve HS include cytotoxic effects, which cause selective cell necrosis, and immunomodulatory effects. The data suggests that if PDT is to be used, it should be with MAL or intralesional ALA. Note that there are a variety of causes of HS. These include hyperkeratosis of in the follicular infundibulum, aberrant cellular immunity, down regulations of defensins in stage III HS, and the infiltration of neutrophils, mast cells, plasma cells, and lymphocytes into the affected follicle, among others. However, it is likely that in individual cases one cause is primary and others secondary. In conclusion, PDT is not a first line treatment for HS but in some cases could be added as an adjuvant to therapies such as clindamycin and rifampin.

Topical treatments of skin pain: a general review with a focus on hidradenitis suppurativa with topical agents.

Hidradenitis Supprurativa (HS) is a painful chronic follicular disease. Few papers have addressed pain control for this debilitating condition. Possible topical agents include tricyclic antidepressants, opioids, anticonvulsants, NSAIDs, NMDA receptor antagonists, local anesthetics and other agents. The first line agents for the topical treatment of the cutaneous pain of HS are diclonefac gel 1% and liposomal xylocaine 4% and 5% cream or 5% ointment. The chief advantage of topical xylocaine is that is quick acting i.e. immediate however with a limited duration of effect 1-2 hours. The use of topical ketamine, which blocks n-methyl-D-aspartate receptors in a non-competitive fashion, might be a useful tool for the treatment of HS pain. Topical doxepin, which available in a 5% commercially preparation (Zonalon®) , makes patients drowsy and is not useful for controlling the pain of HS . Doxepin is available in a 3% or 3.3% concentration (which causes less drowsiness) from compounding pharmacies and can be used in compounded analgesic preparations with positive effect. Topical doxepin is preferred over use of topical amitriptyline because topical doxepin is more effective. Nevertheless, topical amitriptyline increase of the tactile and mechanical nociceptive thresholds and can be used for topical pain control in compound mixture of analgesics . Gabapentin and pregablin can also be used compounded with other agents in topical analgesic preparations with positive topical anesthetic effect. Capsaicin is not useful for topical treatment of the pain of HS. Sometimes compounded of anesthetics medications such as ketamine 10%, bupivacaine 1%, diclofenac 3%, doxepin 3% or 3.3%, and gabapentin 6% can extend the duration of effect so that medication only needs to be used 2 or 3 times a day. Still in my experience the easiest to get and most patient requested agent is topical diclonefac 1% gel.

Dissecting cellulitis (Perifolliculitis Capitis Abscedens et Suffodiens): a comprehensive review focusing on new treatments and findings of the last decade with commentary comparing the therapies and causes of dissecting cellulitis to hidradenitis suppurativa.

Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis abscedens et suffodiens (Hoffman) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. In the U.S., it predominantly occurs in African American men between 20-40 years of age. DC also occurs in other races and women more rarely. DC has been reported worldwide. Older therapies reported effective include: low dose oral zinc, isotretinoin, minocycline, sulfa drugs, tetracycline, prednisone, intralesional triamcinolone, incision and drainage, dapsone, antiandrogens (in women), topical clindamycin, topical isotretinoin, X-ray epilation and ablation, ablative C02 lasers, hair removal lasers (800nm and 694nm), and surgical excision. Newer treatments reported include tumor necrosis factor blockers (TNFB), quinolones, macrolide antibiotics, rifampin, alitretinoin, metronidazole, and high dose zinc sulphate (135-220 mg TID). Isotretinoin seems to provide the best chance at remission, but the number of reports is small, dosing schedules variable, and the long term follow up beyond a year is negligible; treatment failures have been reported. TNFB can succeed when isotretinoin fails, either as monotherapy, or as a bridge to aggressive surgical treatment, but long term data is lacking. Non-medical therapies noted in the last decade include: the 1064 nm laser, ALA-PDT, and modern external beam radiation therapy. Studies that span more than 1 year are lacking. Newer pathologic hair findings include: pigmented casts, black dots, and "3D" yellow dots. Newer associations include: keratitis-ichthyosis-deafness syndrome, Crohn disease and pyoderma gangrenosum. Older associations include arthritis and keratitis. DC is likely a reaction pattern, as is shown by its varied therapeutic successes and failures. The etiology of DC remains enigmatic and DC is distinct from hidradenitis suppurativa, which is shown by their varied responses to therapies and their histologic differences. Like HS, DC likely involves both follicular dysfunction and an aberrant cutaneous immune response to commensal bacteria, such as coagulase negative staphylococci. The incidence of DC is likely under-reported. The literature suggests that now most cases of DC can be treated effectively. However, the lack of clinical studies regarding DC prevents full understanding of the disease and limits the ability to define a consensus treatment algorithm.

An atlas of the morphological manifestations of hidradenitis suppurativa.

This article is dermatological atlas of the morphologic presentations of Hidradenitis Suppurativa (HS). It includes: superficial abscesses (boils, furnucles, carbuncles), abscesses that are subcutaneous and suprafascial, pyogenic granulomas, cysts, painful erythematous papules and plaques, folliculitis, open ulcerations, chronic sinuses, fistulas, sinus tracts, scrotal and genital lyphedema, dermal contractures, keloids (some that are still pitted with follicular ostia), scarring, skin tags, fibrosis, anal fissures, fistulas (i.e. circinate, linear, arcuate), scarring folliculitis of the buttocks (from mild to cigarette-like scarring), condyloma like lesions in intertrigous areas, fishmouth scars, acne inversa, honey-comb scarring, cribiform scarring, tombstone comedones, and morphia-like plaques. HS can co-exist with other follicular diseases such as pilonidal cysts, dissecting cellulitis, acne conglobata, pyoderma gangrenosum, and acanthosis nigricans. In sum, the variety of presentations of HS as shown by these images supports the supposition that HS is a reaction pattern.HS is a follicular based diseased and its manifestations involve a multitude of follicular pathologies [1,2]. It is also known as acne inversa (AI) because of one manifestation that involves the formation of open comedones on areas besides the face. It is as yet unclear why HS is so protean in its manifestations. HS severity is assessed using the Hurley Staging System (Table 1). It also remains unclear why hidradentitis may remain limited to Hurley Stage 1, evolve to the more confluent (Hurley Stage 2), or progress even further to the fully confluent (Hurley Stage 3).In addition, HS can be associated with other follicular based diseases such as pilonidal cysts (PCs) of the sacrum and buttocks, dissecting cellulitis (DC), and acne conglobata (AC), which usually involves the face, chest, When HS occurs with PCs, DC, and/or AC it is referred to as the follicular occlusion triad or tetrad [2]. HS can more rarely be associated with pyoderma gagrenosum (PG) or Crohn disease (CD), other inflammatory diseases of the skin that are not follicular. The reason for this is unclear [2]. What AC, DC, HS, CD, and PG share is that they occur in bacterially rich environments. HS probably occurs with acanthosis nigricans because many HS patients are obese [2]. This concurrence seems under reported.

A multistep approach to improving biopsy site identification in dermatology: physician, staff, and patient roles based on a Delphi consensus.

IMPORTANCE: Excisional skin cancer surgery is a common procedure, with no formal consensus for mitigating the risk of wrong-site cutaneous surgery. OBJECTIVE: To systematically consider the usefulness and feasibility of proposed methods for correct biopsy site identification in dermatology. EVIDENCE REVIEW: Survey study with a formal consensus process. Item development was via a literature review and expert interviews, followed by 2 stages of a Delphi process to develop consensus recommendations. FINDINGS: In total, 2323 articles were reviewed in the literature search, with data extraction from 14. Twenty-five experts underwent 30-minute structured interviews, which were transcribed and coded. The resulting survey was composed of 42 proposed interventions by multiple stakeholders (biopsying physicians, operating physicians, nurses, ancillary staff, patients, caregivers, and family members) at 3 time points (day of biopsy, delay and consultation period, and day of definitive surgery). Two rounds of a Delphi process with 59 experts (25 academic and 34 private practice) scored the survey. Strong consensus was obtained on 14 behaviors, and moderate consensus was obtained on 21 other behaviors. In addition, a 2-state simultaneous algorithm was developed to model surgeon behavior on the day of definitive surgery based on surgeon and patient perceptions. CONCLUSIONS AND RELEVANCE: When definitive surgery is performed after the initial biopsy and by a different surgeon, procedures can be implemented at several time points to increase the likelihood of correct site identification. The specific circumstances of a case suggest which methods may be most appropriate and feasible, and some may be implemented. The risk of wrong-site cutaneous surgery can be reduced but not eliminated.

A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma.

Although rare, severe hidradenitis suppurativa (HS) of the anal, perianal, gluteal, thigh, and groin regions can evolve into squamous cell carcinoma (SCC). This usually does not occur until the HS has been present for more than 20 years. Malignant degeneration of HS in the axilla has not been reported. SCC has developed in dissecting cellulitis, acne conglobata, and pilonidal cysts (other members of the follicular tetrad). Whereas the male to female ratio of HS is 1:3, SCC in HS has a male to female ration of 5:1. The reasons behind malignant degeneration in HS are complex and might differ from the malignant degeneration causing Marjolin ulcers. It likely involves the presence of human papilloma virus (HPV) in affected areas (a rarity in the axilla), and impaired defensins, which combat HPV, in the skin of Hurley Stage III HS. In familial HS, the odds of developing SCC are likely greater because of independent loss-of-function mutations in the γ-secretase multiprotein complex, which regulates the Notch signaling pathway. Compromise of the Notch signaling pathway can undermine immune function and increase the risk of neoplastic development. Coincident SCC with use of tumor necrosis factor α blockers has been reported. I report a patient with long standing Hurley Stage III, familial HS, wwho developed metastatic SCC after 3 courses of infliximab and expired 11 months after the infliximab was started. A 47-year-old male presented with progressive HS since early adulthood. His stage III hidradenitis suppurativa (HS) involved his groin, legs buttocks, and perineal areas. Interestingly, his HS was familial; one daughter also suffered from HS. A pilonidal cyst had been excised in the past. He suffered from hypertension for which he took ramipril, 2.5 mg per day. He did not admit to smoking. He had undergone numerous surgeries and courses of clindamycin with rifampin and clindamycin with minocycline. He used pregablin among other stronger medications for pain control. He had also taken isotretinoin years before without substantial long-term benefit. The various treatments were palliative but the HS always returned. He expressed that the pain from his HS was not bearable. He decided in consultations with his doctors to try infliximab owing to the positive clinical data for its efficacy in HS. He took 3 courses of infliximab 500mg, each of which was followed by surgical debridement of the perineal and anal areas. At the 3rd surgical debridement his physician noted the presence of squamous cell carcinoma (SCC) on July 28, 2008. The infliximab was stopped. However, the patient developed the patient underwent scanning soon after that showed soon after that the SCC had metastasized. He expired in June of 2009.