The successful use of oral apremilast for a case of dissecting cellulitis

Introduction

Dissecting cellulitis of the scalp (DCS), or perifolliculitis capitis abscedens et suffodiens, is a chronic inflammatory dermatosis characterized by painful draining nodules and neutrophilic scarring alopecia of the scalp. The pathophysiology of DCS, similar to hidradenitis suppurativa (HS) and other members of the follicular occlusion tetrad, features follicular occlusion and inflammation, leading to abscess formation with tunnels and interconnected scarring.¹ Treatments for DCS include antibiotics, retinoids, tumor necrosis factor-alpha (TNF-α) inhibitors and surgical modalities.² Apremilast, a phosphodiesterase-4 inhibitor, has shown some efficacy in HS, suggesting it may be effective in DCS.³ We present a case of a patient with long-standing, refractory DCS successfully managed with apremilast.

Case report

A 54-year-old man with a medical history significant for epilepsy, hyperlipidemia, diabetes mellitus, and hypertension presented to the dermatology clinic with a 4-month history of draining sores on his scalp with associated hair loss. At the time of presentation, the patient had already been diagnosed with DCS (including consistent biopsy) and had tried and failed courses of oral erythromycin and minocycline through an outside facility. Physical examination at the initial visit showed several fluctuant, tender nodules throughout the posterior and vertex scalp.

Over the next 5 years, numerous topical and oral treatments were trialed, including 1% clindamycin solution for 4 months, 2.5% selenium sulfide 2.5% wash for 1 year, 0.05% fluocinonide solution for 2 months, trimethoprim-sulfamethoxazole 800/160 mg twice a day for 2 months, minocycline 100 mg twice a day for 3 months, dapsone 100 mg daily for 6 months, and isotretinoin 80 mg daily for 4 months. The patient also was prescribed adalimumab 80 mg every 14 days for 5 months. No significant improvement was seen with any of these treatments, and the patient continued to report new and worsening nodules and cysts on his scalp, along with progressive alopecia. Intralesional triamcinolone injections provided initial improvement but excision and deroofing offered the most satisfactory results. The patient underwent 4 separate deroofing procedures of sinus tracts and cysts throughout the scalp. Despite the benefit of the surgical interventions, the patient’s condition progressed and new, draining nodules continued to form. After the fourth deroofing procedure, at which point he was taking no medications for DCS, apremilast was prescribed.

Six months after starting 30 mg of apremilast twice daily, the patient reported dramatic improvement of disease symptoms and reduction in flares with no notable side effects. Clinical examination revealed only 1 small active area of disease on the left occipital scalp. An additional in-clinic surgical deroofing procedure was performed at the time and apremilast was continued. The patient remains on 30 mg of apremilast twice daily with sustained improvement of his DCS and has not required additional procedures (Fig 1).

Fig 1.

Image on left is of the patient’s posterior scalp before treatment with apremilast and image on right is the patient’s posterior scalp 6 months after starting apremilast and a deroofing surgery.

Discussion

DCS is a chronic inflammatory disease characterized by suppurative nodules and abscesses on the scalp, leading to sinus tract development and associated scarring alopecia. DCS most commonly affects black men around 20 to 40 years of age, though can affect people of other ethnicities as well as less commonly women and children. Treatment varies depending on the stage and severity of disease, and often requires a combination of medical and surgical modalities. Initial therapy typically consists of topical and/or oral antibiotics. Tetracyclines commonly used first-line, though clindamycin, trimethoprim-sulfamethoxazole and dapsone are frequently used as well, among others.^2,4 Isotretinoin is another commonly prescribed therapy for patients with DCS with moderate to severe disease activity; a meta-analysis by Guo et al⁵ showed that DCS patients with DCS on isotretinoin had significant improvement in their disease. However, recurrence was noted in 24% (6/25) of cases.

Apremilast is an oral small molecule inhibitor of phosphodiesterase-4 that exhibits intracellular antiinflammatory properties and has been shown to be effective in various chronic inflammatory diseases. During the stimulus of a pro-inflammatory event, G-protein coupled receptors, via the G protein alpha subunit, activate adenylate cyclase to produce cyclic adenosine monophosphate, a key secondary messenger in the inflammatory cascade. In many white blood cells, cyclic adenosine monophosphate is degraded via hydrolysis by phosphodiesterase-4. By inhibiting this step in the pathway, the resultant increase in intracellular cyclic adenosine monophosphate blocks the production of proinflammatory cytokines such as TNF-α, interferon gamma, and interleukin 2 while increasing the production of the antiinflammatory mediator interleukin 10. This modified pathway also sequesters cyclic adenosine monophosphate response element binding protein from the nuclear factor kappa B pathway leading to a reduction in nuclear factor kappa B dependent gene expression of interleukin 23, TNF-α, and interferon gamma.⁶ Originally Food and Drug Administration approved in 2014 for the use in plaque psoriasis and psoriatic arthritis, and more recently for oral ulcers in Behçet disease,⁷ apremilast has also recently been used off-label for several other inflammatory diseases, including for atopic dermatitis and HS. One randomized controlled trial studying the use of apremilast in 20 patients with HS noted significant results in the reduction of pruritus, numerical rating scale for pain, and overall lower abscess and nodule count.,³ with 8 out of 15 (53.3%) patients treated with apremilast achieving a positive Hidradenitis Suppurativa Clinical Response at week 16.

Conclusion

DCS and HS share many clinical, dermatoscopic, pathologic, and histologic aspects, and are likely varieties of the same disease with differences in appearance attributable to the regionality of follicular and apocrine gland density.⁸ These similarities have supported the treatment of DCS with TNF-α inhibitors which are commonly used to manage HS. Therefore, the established precedence to treat HS and DCS similarly guided the treatment of this patient with apremilast. Limitations of this case report are that it is a single patient and that normal fluctuation of disease cannot be excluded. Further studies of apremilast in DCS including controlled trials are necessary to determine the therapeutic effect. Nevertheless, apremilast is a mechanistically reasonable option for DCS and our report suggests it may have a therapeutic role in managing active inflammation in patients with DCS.

Conflicts of interest

None disclosed.