Noah Scheinfeld

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.

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.

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.

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.

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.

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.

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.