Vascular Proliferation in Biopsies from Active Lichen Planopilaris as a Novel Pathologic Finding

To the Editor: Lichen planopilaris (LPP) is a common type of lymphocytic cicatricial alopecia observed in the hair clinic. It is suspected clinically by the presence of scalp itch or pain associated with single or several hairless patches with follicular dropout, erythema, and follicular hyperkeratosis. The diagnosis is facilitated by using scalp dermoscopy (trichoscopy) to enhance the visualization of the clinical findings and select the optimal biopsy site.1 Classic trichoscopic features include loss of follicular openings, peripilar casts (tubular tight scales) encircling the emergences of single or mini tufts of terminal hairs, and perifollicular erythema, pili torti, and dystrophic hairs.2 The erythema has usually been described as concentric perifollicular dots associated with peripilar casts, or elongated capillaries around a hair follicle opening or at the periphery of the patch,3 and milky white areas in late lesions.4 However, apart from that, the vascular component has been characterized vaguely including in pathology. We have noticed that some patients present with pronounced, patchy, intense “plexiform”-like erythema in an interfollicular distribution. Here, we describe this dermoscopic vascular finding and its pathological correlation in 3 cases of biopsy-proven LPP. CASES Two women in their 60s and 1 man in his 50s presented with diffuse erythematous patches on the parietal scalp and the vertex (n = 2) or localized only to the vertex (n = 1) associated with recalcitrant scalp itch and sensitivity. Two of them had a known history of LPP. They had been experiencing intermittent flares and persistent itch for several years despite different treatment modalities, and one was a new patient. Trichoscopy images were available in 2 cases and revealed interfollicular pink-to-violaceous linear vessels organized in a plexiform network (plexiform-like erythema) (Figs. 1A, B). The plexiform appearance results from the tangled arrangement of the superficial and adventitial cutaneous vascular plexus. Chrysalides were not detected, and there were crystalloids in 1 case (Fig. 1A). Of note, all patients complained of persistent scalp itch and soreness indicative of disease activity. The erythema resolved progressively with treatment, and that correlated with symptom resolution and stabilization of the disease (Fig. 1C). Biopsies obtained using the dermoscopy-guided technique from the patchy erythematous areas were bisected horizontally following the Headington technique.FIGURE 1.: A, Interfollicular erythema in a plexiform pattern in LPP. Note the peripilar casts at the periphery (FotoFinder, 20×). B, Another patient with LPP displaying plexiform erythema. Note crystalloids among the vessels. Peripilar casts are lacking because of using an interface solution (FotoFinder ×20). C, D, Resolution of the erythema with treatment (FotoFinder, ×20). Compare before (C) versus after result (D).Pathology revealed altered follicular architecture with areas of follicular dropout and presence of compound follicles with perifollicular fibrosis and moderately dense lichenoid (2 cases) and interface (1 case) lymphohistiocytic infiltrate (Fig. 2A). One case showed red blood cells tagging at the junction of the follicular epithelium and the dermal stroma (Fig. 2B). We detected increased number of small, thin-walled capillaries organized in clusters in a “vascular sprouting” pattern (Fig. 2C). Most vessels showed congestion and were surrounded by purpuric red blood cells, lymphocytes, and histiocytes. The endothelial lining showed plump nuclei with conspicuous nucleoli and prominent cytoplasm without overt mitotic activity or infiltrative pattern of growth (Fig. 2D). CD31 and D2-40 staining confirmed the dual increased vascular and lymphatic differentiation of the blood vessels (Fig. 2E).FIGURE 2.: A, Lichen planopilaris characterized by compound follicles with perifollicular fibrosis and lichenoid infiltrate (H&E, ×10). B, Red blood cells extravasation and red blood cells tagging the dermo–epidermal junction in the interface dermatitis (H&E, ×20). C, Sprouts of small blood vessels in the dermis, most with congested lumina (H&E, ×20). D, Dilated capillaries with perivascular lymphocytes. Note the plump endothelial cells without atypia (H&E, ×40). E, Focal dual positivity for blood vessels and lymphatics (immunohistochemistry for CD31 and D2-40, ×10).DISCUSSION Our cases highlight the finding of angiogenesis in biopsies from patients with LPP. We consider this an indicator of disease activity. This histology corresponds to the trichoscopic findings of interfollicular plexiform erythema, which has not been previously described. There are previous reports of violaceous erythema with a brown hue attributed to an inflammatory infiltrate with pigment incontinence.3 In our cases, the plexiform arrangement arises from an irregular network of tangled linear vessels without perifollicular accentuation, which distinguishes it from the perifollicular erythema in LPP and the follicular red dots in discoid lupus erythematosus.5 This pattern is due to the combination of ectatic linear vessels in the subpapillary vascular plexus and the proliferation of new small blood vessels at the same level. Similar findings of increased microvascular density and angiogenesis have been shown to play a role in the etiopathogenesis and progression in lesions of oral lichen planus.6 A vicious cycle, in which an inflammatory state promotes angiogenesis, which in turn facilitates chronic inflammation, has been found in some other inflammatory diseases such as bullous pemphigoid, contact dermatitis, rosacea, and psoriasis.7 We believe that the endothelial cell activation and subsequent vascular proliferation in LPP is not incidental, and similarly to oral lichen planus, is driven by inflammatory mediators (such as VEGF and HIF-1 alpha). The angiogenesis in fact has a mechanistic role in the disease activity by: (1) upregulation of adhesions molecules (ICAM-1, VCAM-1, and E-selectins) that can be activated by circulating cytokines; (2) continuous extravasation of inflammatory cells through diapedesis,8 with tissue damage and activation of pain receptors; (3) leaking plasma and proteins through the incomplete endothelial junctions promoting liberation of histamine and prostaglandins associated with edema and pruritus; (4) facilitation of fibroblast activity that turns into scarring in late scenarios.9,10 Histology is crucial in making the diagnosis, as cutaneous angiosarcoma simulating clinically LPP has been described, and its histology can show low-grade features, with proliferation of jagged and dissecting vascular channels in the stroma lined by endothelial cells without significant atypia.11 A careful correlation and histologic evaluation with emphasis on the pattern of growth is recommended. In conclusion, detecting plexiform erythema on trichoscopy in lesions of LPP may indicate disease activity/flare and require aggressive treatment to prevent further progression. In fact, we have observed erythema fade with successful treatment and symptomatic relief (see Fig. 1C). The therapy must lead to involution of angiogenesis, vascular regression, and resorption of inflammatory infiltrates because these are no longer observed in biopsies from patients with stable LPP lesions. In the reported cases, 2 of our patients have been off topical steroids for months before recruitment and one has been naïve to treatment. That, and the fact that erythema resolved progressively with treatment, correlated with symptom resolution and stabilization of the disease, argues in favor of pathogenic correlation versus neurogenic inflammation. A further series of prospectively collected dermoscopy-guided biopsies from plexiform erythema should validate our findings and their significance in the management of LPP. Unfortunately, retrospective review of the vascular pattern in collected LPP biopsies may not be helpful, as it could be biased by the stage of the lesion and by targeted sampling of affected hairs versus interfollicular erythema.