Clinical assessment of the use of topical liquid diclofenac following laser microporation of cutaneous neurofibromas in individuals with neurofibromatosis type 1

Lisa Brauer Oliveira, Mauro Geller, Karin Soares Cunha, Alessandra Santos, Allan Bernacchi, Allan E Rubenstein, Sanyu Takirambudde, Spyros Mezitis, Carolina de Almeida Ito Brum, Luiz Guilherme Darrigo Jr, Marcia Gonçalves Ribeiro, Lisa Brauer Oliveira, Mauro Geller, Karin Soares Cunha, Alessandra Santos, Allan Bernacchi, Allan E Rubenstein, Sanyu Takirambudde, Spyros Mezitis, Carolina de Almeida Ito Brum, Luiz Guilherme Darrigo Jr, Marcia Gonçalves Ribeiro

Abstract

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with a prevalence of 1:3000 births and a wide variety of clinical manifestations. Cutaneous neurofibromas (cNF) are among the most common visible manifestations of NF1 and present a major clinical burden for patients. NF1 patients with cNF often report decreased quality of life, emotional well-being and physical comfort. Developing effective medical therapies for cNF has been identified as a priority for the majority of adults with NF1.

Methods: The study was an open, controlled and prospective proof-of-concept clinical trial. The topical treatment consisted of two steps: cNF microporation using a laser device followed by topical application of one drop of diclofenac 25 mg/mL on the surface of the cNF (T neurofibroma = treatment) or physiological saline (C neurofibroma = control) and reapplied twice daily for 3 days. Neurofibroma assessments included visual and dermatoscopy observations noting color and presence of necrosis, presence of flaccidity, measurements in two dimensions, photographs, and histopathology after excision. The primary efficacy variable was the presence of tissue necrosis. The primary safety variable was the occurrence of treatment-related adverse events.

Results: Six patients were included in the study. The treatment resulted in transitory topical changes (healing of the microporation grid with formation of scintillating tissue layer, hyperemia and desquamation), with no statistically significant variation in the dimensions of the T and C neurofibromas in relation to pretreatment measurements. There was no necrosis in the T or C neurofibromas. In the histopathological analysis, there was no significant difference in the distribution of chronic (lymphocytic) inflammatory infiltrate in the papillary reticular dermis (subepithelial), type of infiltrate (diffuse, perivascular, or both), presence of fibrosis, and presence of atrophy among the T and C neurofibromas. No adverse events attributable to the use of diclofenac were reported during the treatment period.

Conclusions: Treatment did not result in significant alterations in terms of presence of tissue necrosis, size, or histopathological features in the T neurofibromas or in comparison to the C neurofibromas. Topical diclofenac with laser microporation was well-tolerated, with no adverse events attributable to diclofenac reported. Whether these observations are due to minimal systemic and neurofibroma exposure remain to be explored in dosage studies with larger patient groups.

Trial registration: ClinicalTrials.gov (NCT03090971) retrospectively registered March 27, 2017.

Keywords: Cutaneous neurofibroma; Diclofenac; Laser microporation; Neurofibromatosis type 1.

Conflict of interest statement

The authors declare no conflict of interest.

© 2021 The Author(s).

Figures

Figure 1
Figure 1
Sequence of photographs showing a T1 neurofibroma at each study assessment visit. Note Microporation grid at Visit 2 and subsequent desquamation. Neurofibroma and microporation grid appear pallid at Visit 6 in relation to pretreatment. (006 T1).
Figure 2
Figure 2
Sequence of photographs showing a T2 neurofibroma at each study assessment visit. Note Microporation grid at Visit 2 and subsequent desquamation. Neurofibroma appears unaltered at Visit 6 in relation to pretreatment (001 T2).
Figure 3
Figure 3
Sequence of photographs showing a C1 neurofibroma at each study assessment visit. Note Microporation grid at Visit 2 and subsequent desquamation. Neurofibroma appears unaltered at Visit 6 in relation to pretreatment (002 C1).
Figure 4
Figure 4
Sequence of photographs showing a C2 neurofibroma at each study assessment visit. Note Microporation grid at Visit 2 and subsequent desquamation. Neurofibroma appears unaltered at Visit 6 in relation to pretreatment (004 C2).

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Source: PubMed

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