Comment on Topical Dapsone for Folliculitis Decalvans

ABSTRACT

Folliculitis decalvans (FD) represents a chronic and recurrent pustulofollicular scalp inflammation resulting in scarring alopecia. The presence of a bacterial bioflilm at the interface of the hair shaft may provide an explanation for the chronicity and high relapse rate of FD, even after prolonged systemic antibiotic treatments. We originally read with enthusiasm Melián-Olivera et al.’s retrospective study of patients with FD treated with topical dapsone published in the Journal of the American Academy of Dermatology. However, we experienced an unsuccessful trial of 5% dapsone gel in a patient with FD resulting in worsening of the disease with a pustular flareup and questioned why positive study reports with novel therapeutic options in dermatology often fail in practice. The authors admitted the limitations of their study: small sample size, retrospective, uncontrolled nature of the study, and concomitant use of other treatments. Clinical research ultimately aims at improving the patient outcome. For this purpose, trials must evaluate the outcomes that genuinely reflect the clinical utility of drugs. Therefore, we postulate stricter criteria for treatment trials and statistics in dermatology before publication in peer-reviewed scientific journals to avoid frustrations of physicians and patients alike.

“Pulling bad science apart is the best teaching gimmick I know for explaining how good science really works.”

- Ben Goldacre

Folliculitis decalvans (FD) represents a chronic and recurrent pustulofollicular scalp inflammation resulting in scarring alopecia. It usually presents in the central scalp area with exsudative crusted areas and grouped follicular pustules at the hair-bearing margin with centrifugal progression. Histopathology reveals a neutrophilic primary scarring alopecia. Invariably pathogenic strains of Staphylococcus aureus are detected.

A report provided evidence of the presence of bacterial biofilms in the infrainfundibular part of human scalp hair follicles to be pathogenic.[1] A biofilm is any group of microorganisms in which cells stick to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance. Biofilms form on living or nonliving surfaces and in the case of FD on the surfaces of the hair shaft. Bacteria living in a biofilm usually have significantly different properties from free-floating bacteria of the same species, as the dense and protected environment of the film allows them to cooperate and interact in various ways. One benefit of this environment is increased resistance to antibiotics, as the dense extracellular matrix and the outer layer of cells protect the interior of the community. Biofilms have been found to be involved in a wide variety of microbial infections in the body, and more recently, it has been noted that bacterial biofilms may impair cutaneous wound healing and reduce topical antibacterial efficiency in healing or treating infected skin wounds.

The presence of a bacterial bioflilm at the interface of the hair shaft may provide an explanation for the chronicity and high relapse rate of FD, even after prolonged systemic antibiotic treatments.

We originally read with enthusiasm Melián-Olivera et al.’s retrospective study of patients with FD treated with topical dapsone published in the Journal of the American Academy of Dermatology.[2] Dapsone is understood to be effective in treating diseases characterized by abnormal neutrophil recruitment.[3] Patients were prescribed 5% dapsone gel three times weekly. To assess the efficacy of treatment, the number of flareups and of months treatment with an oral antibiotic before and after introducing dapsone was recorded. A flareup was defined as clinical worsening of disease with need for an oral antibiotic. Fourteen patients were included who received topical dapsone for a mean time of 30 months. A median of 0.13 flareups per month took place before the administration of dapsone gel, whereas the frequency after its introduction was 0.03. This reduction was considered as statistically significant to consider topical dapsone a promising regimen for reducing the number of outbreaks in FD. The authors noted that in three patients there was a change over to the FD-lichen planopilaris (FD-LPP) phenotypic spectrum during the treatment.

FD-LPP phenotypic spectrum is characterized as bi-phasic presentation of FD and LPP, which the original authors of the condition recognized to be more common than expected from the paucity of reports in the literature. With regard to its etiopathogenesis, they hypothesized an abnormal hair follicle immune response, that may be related to alterations of the residential microbiome resulting in a Th1-mediated inflammation and permanent hair follicle damage.[4]

In fact, we were the first to report on the bi-phasic nature of FD based on sequential dermoscopic examination in FD and proposed that the development of features of LPP with time may be due to the disruption of hair follicles in the course of bacterial infection, with exposure of follicular antigens ultimately giving rise to autoimmunity targeting the hair follicle at critical sites.[5] Therefore, the phenotypic presentation that is classified here as FD-LPP phenotypic spectrum is rather just the manifestation of a final common pathway seen in diverse scarring alopecias, including FD. Therefore, the term secondary LPP-like changes in FD may be more appropriate than FD-LPP phenotypic spectrum, and in our opinion, the condition seems to represent the natural course of FD. Conventionally, in this later phase of disease, FD becomes lichenoid in character with fewer pustular flareups and lesser need of antibiotics.

Given the mean treatment time of 30 months with topical dapsone in Melián-Olivera et al.’s study, it seems apparent that the lesser frequency of flareups may simply be explained through the natural course of disease rather than the treatment.

After a recent unsuccessful trial of 5% dapsone gel daily during 6 weeks in a patient with FD resulting in worsening of the disease with a pustular flareup [Figure 1a and b], we categorically questioned why positive study reports with novel therapeutic options in dermatology often fail in practice.[6]

Figure 1.

Folliculitis decalvans (a) before, and (b) after 6 weeks treatment with 5% dapsone gel daily. Worsening with pustular flareup

The authors admitted the limitations of their study: small sample size, retrospective, uncontrolled nature of the study, and concomitant use of other treatments. However, clinical research ultimately aims at improving patient outcome. For this purpose, trials must evaluate outcomes that genuinely reflect clinical utility of drugs.[7] Therefore, we postulate stricter criteria for treatment trials and statistics in dermatology before the publication in peer-reviewed scientific journals to avoid frustrations of physicians and patients alike.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.