I wrote about Hidradenitis Suppurativa in an earlier post. Of interest is a recent NEJM article on the use of Adalimumab for the treatment of this horrible disease.
In the phase three trial:
Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001).
In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12.
The use of this TNF-alpha inhibitor demonstrated efficacy, but not a cure for this scarring and painful disease. Significant improvement was noted in the rank ordered secondary outcomes of lesion count, pain score, and disease severity.
The wording goes:
In conclusion, these two randomized trials involving patients with moderate-to-severe hidradenitis suppurativa showed that adalimumab substantially increased the likelihood of a clinically significant response at week 12, as defined by at least a 50% reduction from baseline in the total abscess and inflammatory-nodule count and no increase in abscess or draining-fistula counts, with or without continued antibiotic treatment.
HS is a chronic inflammatory skin disease associated with the formation of multiple abscesses, nodules, and scars in the apocrine gland-bearing areas. Sites that are affected include inguinofemoral (groin), axillary (arm pit) , perianal, gluteal (buttocks) , and submammary (breast) regions. Approximately 1-4% of the population is affected by this disorder. The apocrine (sweat) glands get occluded by hyperkeratotic (skin material) debris that produce follicles that rupture and cause inflammation.
The course of HS can vary from small pustules to inflammatory nodules, and in some cases become inflammatory, deep abscesses and draining sinus tracts. In other words, an infected pock marked mess.
This disease is staged in to three categories with Stage 1 being basic abscesses without scarring and Stage 3 being the worst, having destroyed completely an area with multiple abscesses that can be interconnected and have sinus tracts (holes) connected to the skin surface.
For those with this disorder, wearing loose fitting clothes that don’t rub the areas involved, not pinching the lesions, wearing antiperspirants but not applying perfumes to the area are helpful. Topical anti-bacterial cleansing with Triclosan-containing soaps will decrease bacterial colonization. Don’t scrub the area when washing as that will inflame the lesions more.
Primary treatment includes quitting smoking – which is highly associated with Hidradenitis Suppurativa. If you continue to smoke, don’t expect to get better. Also weight loss is important as 2/3 of those with HS are overweight. The HS may be due to elevated insulin levels, hormonal changes, and dietary problems in these individuals. Avoiding dairy and high glycemic loaded foods can decrease the disease.
Metformin, an anti-diabetic drug can be helpful in decreasing the HS disease burden. This is a result of the insulin-sensitizing effect of Metformin as it is believed that HS results, in part, from elevated insulin levels.
Treatment methods, after the basics listed above, include the use of Resorcinol, a chemical peeling agent, which as a 15% solution and applied twice a day, can improve the HS lesions and decrease pain and inflammation.
Also used are antibiotics, usually Doxycycline and minocycline first line, then Clindamycin if those are not helpful. Clindamycin mixed with Rifampin has been effective in 2/3 of patients with moderate disease. Some physicians use a combination of Moxifloxacin, Rifampin, and Metronidazole with good success.
Dapsone, an antibiotic with immunomodulatory effect, has had effect in early stage disease.
Intralesional injection of steroids is another option for local treatment as a monthly injection over a period of three months or so. Occasionally surgery must be done or an incision and drainage when a large abscess forms.
Androgens can promote the development of HS. It has been found that drospirenone- (or norgestimate-) containing oral contraceptives with spironolactone ( a blood pressure medication with anti-androgen effects) has been helpful in women.
For patients who don’t want to quit smoking or cannot lose weight and for those who fail other medical therapies, anti-TNF (tumor necrosis factor) agents are effective and have been approved for use in HS. The injected agent Infliximab was found to have a 50% reduction in severity score with most having improvement in pain and quality of life. Adalimumab was recently FDA approved for HS treatment but has been less effective. Whereas Infliximab is administered by weekly infusions, Adlimumab is given by subcutaneous weekly injections. The problems with the anti- TNF agents include risks for infection, heart failure, demyelinating disease, a lupus-like syndrome, and malignancy.
Oral retinoids such as acitretin and Isotretinoin have shown beneficial effect as well. Acitretin given as 0.6 mg/kg daily for 9 to 12 months showed highly effective in diminishing the disease, an effect that remained after the medicine was stopped, unlike with the biological agents, which have a higher relapse rate after discontinuance. Isotretinoin also has been effective in several studies with lower relapse after discontinuance. Both agents are highly teratogenic.
Systemic prednisone can decrease inflammation when given over 7-10 days at 40 mg a day. Cyclosporine has also been used as well.
Vitamin D3 supplementation at 300-6000 Units daily has been helpful in decreasing HS lesions in some individuals.
Zinc salts have antiinflammatory and antiandrogenic properties. Zinc Gluconate at 90 mg daily was very effective (36%) in significantly decreasing the inflammation of low grade HS, with beneficial effect in most who use zinc supplements.
What is interesting about Hidradenitis Suppurativa, is the inflammatory component of the disease. We know that the risk of the disease increases with obesity and cigarette smoking, which are also associated with elevated markers of inflammation themselves. Obesity is associated with elevated inflammatory markers and insulin levels, which appear to play a role in the genesis of HS as well as other diseases (i.e hypertension, fatty liver, diabetes, cancer, etc) In the article listed below, it was recognized that HS and the risk of it’s progression can be estimated by CRP levels, a marker of total body inflammation. CRP is produced by the liver in response to IL-6, another inflammatory marker. This generalized inflammation affects multiple organ systems.
The above study examined the use of CRP and white blood count (wbc) in estimating the risk of progression and inflammatory content of patients with various stages of HS.
The study found that CRP level and neutrophil counts are effective tools for assessing the extent of disease severity and grade of inflammation in patients with HS above and beyond the association of these inflammatory markers with coincidental comorbidities. For example, obese patient have elevations in CRP and smokers have higher white blood cell counts, but this study showed that CRP and wbc independently predicted worse disease status in patients with HS. There was a significant correlation between these inflammatory serum markers and disease severity according to HS severity grading scale. The end finding is that CRP is a significant and independent predictor for severe disease activity of Hidradenitis Suppurativa.
What interests me about this disease is it’s associations with comorbidities. Smokers have little hope of remission of HS and HS is associated strongly with obesity. These same disorders are inflammatory in their own right. It is felt that the elevated levels of insulin and insulin resistance in obesity may play a role in worsening of HS. Obesity and the hormonal catastrophe associated with it is also associated with coronary heart disease, hypertension, fatty liver, and a host of other life-limiting diseases. So again, here is a disease process (HS) that is, in part, partially a creature of our own design – bad habits. If we could stop smoking and limit obesity, how much HS would really exist?