Abstract
Linear psoriasis is an unusual clinical variation of psoriasis that manifests segmentally along the lines of Blaschko. A major differential diagnosis is inflammatory linear verrucous epidermal nevus (ILVEN). The treatment of linear psoriasis is often challenging, with inadequate response to biological agents reported in the literature. We report a case of a 25-year-old African-American female who presented with asymptomatic hyperkeratotic papules along the lines of Blaschko and was subsequently diagnosed with linear psoriasis. After failing conventional treatment regimens, the patient received a trial of ixekizumab with complete resolution of cutaneous lesions reported after 4 months and only 8 doses of the anti-IL-17 biologic agent.
1. Introduction
Linear psoriasis is a rare clinical variation of psoriasis that manifests segmentally along the lines of Blaschko. The pathogenesis remains unclear, though some have proposed it could be explained by the well-established concept of genetic mosaicism [1]. Happle (1991) suggested that the loss of heterozygosity in somatic cells during early embryogenesis results in somatic recombination with daughter cells. Subsequently, these daughter cells go on to become clonal stem cells proliferating in a linear pattern during the embryonic development of the skin. A major differential diagnosis for linear psoriasis is inflammatory linear verrucous epidermal nevus (ILVEN), which also presents along the lines of Blaschko with similar morphology [2]. Psoriasis presenting in this manner is often mistaken for ILVEN and undertreated. The treatment of linear psoriasis can be challenging, with reports of inadequate clinical response to various biologic agents approved for the treatment of plaque psoriasis [3]. To our knowledge, we report the first case of this atypical psoriasis morphology successfully treated with the biologic agent ixekizumab.
2. Case Report
A 25-year-old African-American female presented to our clinic with asymptomatic lesions linearly arranged over her left upper extremity. The initial lesion first appeared fifteen years ago and new lesions gradually appeared over time. She denied joint pain and/or a history of infections prior to lesion development. Her past medical history was significant only for posttraumatic distress disorder and depression. There was no personal or family history of psoriasis or other dermatologic disease. Prior to presentation in our clinic, she had a skin biopsy of the right forearm which showed chronic spongiotic dermatitis with parakeratotic foci and superficial perivascular mononuclear infiltrates. No deep dermal or periadnexal infiltrates were seen and periodic acid-Schiff staining was negative for fungal organisms. Based on the results, both lichen striatus and linear psoriasis were considered as potential diagnosis, and she was started on high-potency topical steroids. A month later, the patient was referred to our clinic when she failed to respond to treatment.
Physical examination revealed hyperkeratotic and scaly gray papules coalescing into a linear plaque of the right dorsal fifth finger extending medially to the right elbow (Figure 1(a)). Of note, scaly papules were also present on a tattoo above the right elbow (Figure 1(b)). There was no nail or palmoplantar involvement. The differential diagnosis included linear psoriasis and ILVEN. The isomorphic reaction seen within the patient’s tattoo (Koebner phenomenon) favored a diagnosis of psoriasis. A skin biopsy and electrodessication of one papule on her right dorsal fifth finger were performed. Histological examination of the specimen revealed parakeratosis with uniformly acanthotic epidermis (Figure 2). At a follow-up visit 2 weeks later, the patient developed new papules with similar morphology in the area that was previously electrodessicated (Figure 3(a)). This new episode of Koebnerization and histological findings further supported our diagnosis of linear psoriasis and the decision was made to initiate treatment with ixekizumab, a monoclonal antibody targeting interleukin- (IL-) 17A. Four months later and after 8 doses of ixekizumab, we observed almost-complete resolution of the cutaneous lesions (Figures 3(b) and 3(c)).
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3. Case Discussion
Linear psoriasis is a rare clinical presentation of psoriasis characterized by the linear distribution of psoriatic lesions along the lines of Blaschko. The main differential diagnosis is ILVEN. Gross morphological distinction between these two entities is difficult. Furthermore, the two entities share similar histological findings and the coexistence of ILVEN and psoriasis has also been reported [3, 4]. Histological examination of ILVEN shows areas of hypergranulosis and orthokeratosis alternating with areas of hypogranulosis and parakeratosis [5]. Under these circumstances, immunohistochemical studies are helpful in distinguishing these two cutaneous disorders. For example, involucrin is a marker whose expression is absent in the parakeratotic areas of ILVEN but present in psoriasis [6]. Moreover, the number of Ki-67 positive nuclei is higher in psoriasis compared to ILVEN, while the number of keratin-10 positive cells is higher in ILVEN [7]. In practice, these tests are rarely ordered. It is often more practical to simply initiate therapy for psoriasis if the diagnosis is suspected.
We are now able to conclude that linear psoriasis was the correct diagnosis in this case based on several observations. First, our patient’s lesions were nonpruritic, and ILVEN tends to be more pruritic than psoriatic lesions [8]. Additionally, Koebner phenomenon affects 25–30% of patients with psoriasis [9], and our patient developed lesions on her tattoo and on the electrodessicated site of her right dorsal hand. To our knowledge, Koebner phenomenon has not been described in any reported case of ILVEN. Finally, ILVEN responds minimally to antipsoriatic agents, and our patient had a remarkable response to only 8 doses of the biologic agent ixekizumab, a drug approved by the US Food and Drug Administration in 2016 for the treatment for moderate to severe plaque psoriasis.
It is known from a small number of reports that segmental manifestations of psoriasis respond less favorably to systemic therapies such as methotrexate, acitretin, and, more recently, biologics [3, 10–13]. The chronicity and resistance of linear psoriasis to available antipsoriatic agents were suggested to be in part due to the loss of heterozygosity in cells where the lesions occur [12]. In our literature review, patients treated with either anti-IL-23 or tumor necrosis-alpha inhibitor agents had significant improvements on all of the types of psoriasis except in linear psoriasis (Table 1). Multiple studies have also demonstrated that even though psoriatic lesions might look similar, they differ substantially in the activation status of inflammatory and cytokine pathways and such networks might contribute to the different treatment responses observed with biologic agents [14]. Furthermore, by analyzing psoriasis transcriptosome in nontreated biopsied lesions, one study was able to differentiate between etanercept responders and nonresponders [15]. This heterogeneity in response further underscores the potential role of gene-expression profiling as potential predictors of response to biologics. There are no current formal guidelines for the treatment of linear psoriasis, and larger studies are needed to determine optimal therapy for this rare variant. In our case, the patient responded favorably to ixekizumab, which opens the possibility of using new biologic agents and individualized therapy in patients with recalcitrant linear psoriasis.
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this paper.