Bullous Lichen Planus Treated with Adalimumab: A Case Report

Bullous lichen planus is uncommon subtype of lichen planus that characterized by vesicles-bullous lesions develop in the context of preexisting lichen planus lesions. Clinically, bullous lichen planus lesions presented as violaceous bullae associated with burning sensation and pain. The exact prevalence of bullous lichen planus remains unknown, and it is usually sporadic [1]. Lichen planus lesions commonly appear on the oral mucosa as an intact bullae or eroded surface superimposed with white striae [2]. There are two variants of bullous lichen planus: familial and nonfamilial. The familial variant is more common, occuring at an earlier age with longer duration of disease and more extensive eruptions with higher tendency of nail involvement [3]. Histologically, lichen planus consists of hyperkeratosis, increased, acanthosis with “sawtooth” appearance, liquefaction of basal cell layer, and presence of band-like inflammatory cell infiltrate at the dermoepidermal junction as well as presence of colloid or civatte bodies at the lower dermis and superficial epidermis. In bullous lichen planus, there is intense lichenoid inflammation and significant epidermal damage with formation of large Max-Joseph spaces between the epidermis and the dermis that alters the dermoepidermal junction and causes liquefactive eruption of the basal layer cells. Bullous lichen planus is often misdiagnosed and should be differentiated from other subepidermal bullous diseases especially lichen planus pemphigoids that have circulating IgG autoantibodies directed against the 180 kDa bullous pemphigoids antigen (BP180; BPAG2), as in idiopathic bullous pemphigoids [1].

Treatment of bullous lichen planus is challenging as only few cases have been published in the literature. Our case demonstrates first complete resolution of bullous lichen planus that was successfully treated with adalimumab in which other therapies were not effective. The CARE checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000543523).

A 46-year-old female, not known to have any medical disease, presented to our outpatient clinic with multiple pruritic, violaceous, coalescent papules and bullae involving lower extremities and oral mucosa for 8 years. Patient denied any history of febrile illness, weight loss, or exacerbation of the eruption with sun exposure. The patient did not take any drugs. The patient was treated at other dermatology clinic for multiple years before coming to our clinic. During that time, she received multiple courses of systemic corticosteroids with no improvement. On clinical examination, the following lesions were found, large well-demarcated violaceous, coalescent tense bullae filled with clear fluid over both palms (Fig. 1a), both dorsal aspect of distal leg (Fig. 1c) and sole (Fig. 1d), small crusted papule over upper lip, small erythematous eroded lesion over left buccal mucosa, sublingual area, small white striae over hard palate, amalgam teeth filling (Fig. 1b). Nails and hair were unremarkable.

Her hepatitis B virus and hepatitis C virus serology screening test were negative, and liver function test was normal. A 4-mm punch biopsy was obtained from a tensed bullous lesion overlying an erythematous papule in right shin. Histological examination revealed band-like lymphohistiocytic infiltrate with saw tooth rete ridges and focal subepidermal cleft formation. No evidence of pemphigus disease, vasculitis, Behcet’s disease, or subcorneal pustular dermatosis. Direct immunofluorescence studies for IgG, IgM, IgA, C3, and fibrinogen were all negative (Fig. 2a, b). Based on clinical and histological findings, a diagnosis of bullous lichen planus was made.

Initially, patient received both oral and topical corticosteroid. She was treated with oral prednisolone 40 mg daily for 4 weeks then tapered 5 mg every week and triamcinolone acetonide 0.1% paste. A slight improvement was noted regarding the cutaneous lesions, however, with relapse upon steroid discontinuation and no response for oral lesions. Furthermore, dapsone 100 mg daily has been tried for 8 weeks with no improvement. Acitretin was not an option because of childbearing age.

As the treatment was not effective, we desired to start an alternative therapy, and we planned to start adalimumab therapy. Prior treatment investigation ordered including complete blood count, liver function test, renal function, and QuantiFERON tuberculosis test were all unremarkable. Adalimumab was started at loading dose of 80 mg subcutaneous at week 1, then 40 mg subcutaneous at week 2, followed by 40 mg subcutaneous every 2 weeks. After 4 weeks of adalimumab treatment, the patient noticed improvement of her lesions on the extremities and the oral mucosa improved in appearance. The severe lesion on the dorsal aspect of the leg began to thin and clear, and by week 8, the patient demonstrated 50% improvement of lesion with no appearing of new lesions. After she completed 20 weeks of adalimumab administration, she showed marked improvement of both mucosal and cutaneous lesions with almost complete resolution (Fig. 3). The treatment benefit of adalimumab reached a plateau with an almost clear response at week 20, in which the oral lesions and the lesions on the distal extremities had substantially cleared.

Up to now, our patient maintained an almost clear response of all lesions for more than 40 weeks of adalimumab therapy. However, the patient did not experience any flare during adalimumab therapy, and no adverse events were noted during treatment. The patient has not experienced serious infections, tuberculosis, congestive heart failure, lymphomas, skin cancers, or solid tumors.

Up to date, there is no established treatment of choice or effective treatment for bullous lichen planus. Considering that bullous lichen planus is a hyperreactive form of lichen planus, topical potent corticosteroids have been used empirically. Systemic corticosteroids have been described as second-line treatments for moderate to severe lichen planus that are refractory to local treatments. A few case reports suggest high efficacy of dapsone in pediatric bullous lichen planus. Other treatment options are antimalarial drugs and acitretin [4]. Adalimumab, a fully human IgG1 against tumor necrosis factor alpha (TNF-α) monoclonal antibody binds to soluble and membrane-bound TNF, thereby blocking TNF activity. The use of TNF-α inhibitor biologics for the management of cutaneous and mucosal lichen planus has been previously described in the literature [5, 6]. A study investigated the possible role TNF-α in the pathogenesis of lichen planus revealed that TNF-α might play a key role in the pathogenesis. There are increased numbers of CD4+ and Langerhans cells in lichen planus lesions. CD4+ cells are activated by antigens associated with MHC class II molecules. Subsequently, CD4+ cells activate CD8+ cells through receptor interaction and by the concurrent action of IL-2 and IFN-γ, and in turn, IFN-γ induces the production of TNF-α from keratinocytes, resulting in increased interaction with T helper cells. Furthermore, the serum TNF-α level is high in the lichen planus patients; however, this is not associated with oral mucosal involvement and gender [7]. Hence, the use of TNF-α inhibitor in management of cutaneous and mucosal lichen planus has been previously described in the literature. Also, in one case report, etanercept was found to be beneficial for oral lichen planus [8].

Furthermore, our case study further confirms that TNF-α inhibitors might be effective in the treatment of bullous lichen planus after other treatments had failed. Adalimumab treatment helped this patient to control her bullous lichen planus better than any prior therapy. Control of bullous lichen planus with adalimumab has permitted our patient to resume normal activities of daily living and improve her quality of life and oral intake. More importantly, adalimumab has reduced her long-term exposure to systemic steroids.

Our case illustrates that adalimumab may represent a promising, efficacious, and safe monotherapy option for the management of bullous lichen planus. The therapeutic value of this novel off-label use should be assessed in controlled clinical trials.

The authors would like to thank the patient for consenting to publication.

Written informed consent was obtained from the patient for publication of the details of her medical case and any accompanying images. The patient has granted his permission in the form for photographs and other clinical data to be published in the publication. The patient is aware that every attempt will be made to maintain anonymity and that neither name nor initials will be published. Ethical approval is not required for this study in accordance with local or national guidelines.

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The authors received no financial support for the research, authorship, and/or publication of this article.

Bashayr S. Alhubayshi and Asem Shadid drafted the manuscript and edited the manuscript. Ahmed A. Alhumidi performed the histopathology slide and wrote the description. Abdulaziz A. Alnoshan collected the clinical data.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.