Laser-assisted delivery of imiquimod in Brooke-Spiegler syndrome

. Romero FT, Pinilla-Martín B, Pérez SIP. Infective dermatitis associated with HTLV-1: dermatosis to be considered in patients from endemic areas. Aten Primaria. 2020;52:785--6. . Bravo FG. Infective dermatitis: a purely cutaneous manifestation of HTLV-1 infection. Semin Diagn Pathol. 2020;37:92--7. . Grenade LL, Manns A, Fletcher V, Derm D, Carberry C, Hanchard B, et al. Clinical, pathologic, and immunologic features of human T-lymphotropic virus type I-associated infective dermatitis in children. Arch Dermatol. 1998;134:439--44.

Initially, the prominent lesions on the left nasolabial sulcus skin were ablated by full-field erbium: YAG laser applied at the setting of 3-mm spot-size, 6 J/cm 2 , 10 Hz with 100 sn pulse duration (Fotona, XS, Dynamis). Due to the requirement of sedoanalgesia for the remaining lesions, she was offered fractional erbium: YAG laser and topical imiquimod combination.
The pre-determined 4-week treatment cycles were repeated for 6-months as monthly Ablative Fractional Laser (AFL) applications immediately followed by imiquimod cream applied 5 consecutive days per week for the first 2-weeks. This was followed by a treatment-free period of 2-weeks. Severe irritation occurred that subsided during treatment-free periods. On 6-months control, her selfreported score changed from 10 to 0 for the part treated with full-field resurfacing and 10 to 2 for the parts treated with a combination of AFL and imiquimod (Fig. 1). She has been under follow-up for 1.5 years without recurrence (Fig. 1B, Fig. 2B).
BSS is an autosomal dominant disorder characterized by progressive, stigmatizing benign cutaneous neoplasms localized on the facial skin and the scalp.
Surgical excision and alternative destructive modalities were reported for BSS skin neoplasms. 1 The ideal goal of interventions is to remove lesions without scarring and dyspigmentation, still yet efficacious enough to prevent recurrences. Recently, topical sirolimus and imiquimod treatments were suggested as non-invasive approaches. 1---4 ଝ Study conducted at the University of Health Sciences, Gulhane Training and Research Hospital, Department of Dermatology, Ankara, Turkey.
The first observation on the efficacy of imiquimod was reported in a case with Multiple Facial Trichoepitheliomas (MFT). 4 Topical tretinoin was introduced in the 6 th month to improve the penetration of imiquimod. This combination was continued till 3 rd year. A retrospective study reported partial response after 32-weeks of imiquimod treatment in two BSS patients. 2 These treatment durations are significantly longer when compared to the approved indications of imiquimod (Table 1). In a single-subject case study, the efficacy of various treatments was evaluated. Two sites received either imiquimod or the combination of AFL and imiquimod. On the 3 rd month, topical imiquimod wasn't   effective. The treatment result of AFL and imiquimod was also similar to AFL alone. An important difference from the combination design is that imiquimod wasn't applied immediately, instead 2 days after AFL. 1 AFL is shown to increase imiquimod flux 46 to 127-fold through multiple passes. 5 Immediate application of the topical agent is central to treatment success of Laser-Assisted Delivery (LAD) which may explain discrepancies in treatment results. A limitation of current observation is that AFL alone can provide similar results, which cannot be compared to the combination therapy defined for this case. However, it should be emphasized that the lack of recurrence on long-term follow-up is extremely rare for Brooke-Spiegler syndrome and the detected results are remarkable.
As imiquimod requires extended treatment durations for trichoepitheliomas, LAD can assist in decreasing the duration. Another important consideration about this regimen is the lack of recurrence on long-term follow-up.

Financial support
None declared.

Authors' contributions
Aysenur Botsali: Approval of the final version of the manuscript; Critical literature review; Data collection, analysis, and interpretation; Effective participation in research orientation; Intellectual participation in propaedeutic and/or therapeutic management of studied cases; Preparation and writing of the manuscript; Study conception and planning.
Ercan Caliskan: Approval of the final version of the manuscript; Critical literature review; Effective participation in research orientation; Intellectual participation in propaedeutic and/or therapeutic management of studied cases; Manuscript critical review; Study conception and planning.

Conflicts of interest
None declared.

Dear Editor,
A 58-year-old female visited our department, complaining of asymptomatic skin lesions on the lower legs, which had appeared two years previously. She did not have diabetes; however, she had been diagnosed as having a goiter at almost the same time as when the skin lesions began and were under follow-up. Physical examination showed several well-circumscribed waxy brownish infiltrated plaques with elevated borders on the bilateral shins ( Fig. 1A and  1B). Initial lesion arose on a burn scar, which had originally been caused by a Japanese electric foot warmer, that is used in the bed in winter. Thereafter, similar lesions were increased in number in the surrounding areas and spread to another lower leg. Laboratory examination showed normal liver and renal function; however, anti-thyroglobulin antibody (209.2 IU/mL; normal <28) and anti-thyroid peroxidase antibody (269.1 IU/mL, normal <16) were elevated. Thyroid Stimulating Hormone (TSH), TSH receptor antibody, and free T3 and T4 thyroid hormones were all within normal limits. Histological examination revealed necrobiotic changes of collagen in the dermis, surrounded by granulomatous inflammatory reactions composed of lymphocytes, histiocytes, and multinucleated giant cells ( Fig. 2A). Of note, lymphoid aggregates were observed at the periphery of the degenerated collagen in the lower dermis. Immunohistological examination showed intense expression of CD3+ T-cells (Fig. 2B) and CD20+ B-cells (Fig. 2C). High endothelial venules-associated pNAd (MECA-79) epitopes were observed