Clinical, Cosmetic and Investigational Dermatology Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Clinical Approach to Linear Hyperpigmentation: A Review Article This article was published in the following Dove Press journal: Clinical, Cosmetic and Investigational Dermatology Mohammad S Alkhowailed 1 Abstract: Linear hyperpigmentation is an unusual anatomical configuration in clinical Mojahed Otayf2 dermatology. Owing to its rarity, consensus on the most effective method of classification Abdulrahman Albasseet2 is lacking. While linear hyperpigmentation generally follows Blaschko’s lines, this is not Abdullah Almousa2 universal. Clinical findings such as adherence to Blaschko’s lines, associated morphological Ziyad Alajlan2 findings (including other cutaneous lesions), and systemic manifestations can be used to further characterize and diagnose variants of the disorder. Early detection of any underlying Saad Altalhab3 disease is vital, especially in cases with effective management, because the disorder may 1Department of Dermatology, College of make it difficult to manage hyperpigmentation. Herein, we introduce a logical clinical Medicine, Qassim University, Buraydah, Qassim, Saudi Arabia; 2College of diagnostic approach that represents a useful tool for dermatologists to efficiently evaluate Medicine, King Saud University, Riyadh, patients presenting with linear hyperpigmentation. A simplified systematic and evidence- 3 Saudi Arabia; Department of based approach is useful for this clinical condition owing to the heterogeneous causes and Dermatology, College of Medicine, Al- Imam Mohammad Ibn Saud Islamic lack of specific diagnostic tools. University, Riyadh, Saudi Arabia Keywords: approach, blaschkitis, Blaschko’s lines, hyperpigmentation, linear, pigmentary mosaicism Key Points Linear hyperpigmentation is a rare anatomical configuration in clinical dermatol­ ogy. Reaching the diagnosis in such presentation is relatively difficult as there is a wide range of differential diagnoses. Creating a classification of linear hyperpig­ mentation will help dermatologists to reach the diagnosis and recognize and avoid potential systemic complications. Introduction Cutaneous hyperpigmentation is a common complaint in dermatologic practice. Clinically, it is classified into diffuse, circumscribed, linear, or reticulated variants. The configuration of the lesion is important to reach the correct diagnosis. Linear hyperpigmentation often has a diagnostic challenge in clinical practice. Various causes including post-inflammatory changes, drug reactions, and mosaic genetic alterations result in hyperpigmentation along Blaschko’s lines. Pigmentary demar­ cation lines represent the normal dorsal–ventral skin patterning. Blaschko’s lines are attributed to the migration lines of epidermal cells during embryogenesis and Correspondence: Mohammad S are characterized by a V-shaped pattern on the posterior midline, S-shape on the Alkhowailed 1,2 Department of Dermatology College of abdomen, and spiral on the posterior scalp. To the best of our knowledge, there is Medicine, Qassim University, Buraidah no existing clinical approach for linear hyperpigmentation diagnosis. We provide a 52571, Qassim, Saudi Arabia Email [email protected] simplified approach for the diagnosis of linear hyperpigmentation through two submit your manuscript | www.dovepress.com Clinical, Cosmetic and Investigational Dermatology 2021:14 23–35 23 DovePress © 2021 Alkhowailed et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/ http://doi.org/10.2147/CCID.S280819 terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Alkhowailed et al Dovepress steps:1 To determine whether hyperpigmentation follows There are many treatment modalities for LPP, but the Blaschko’s lines;2 to determine the presence or absence of current first-line therapy includes high-potency topical and associated systemic manifestations in addition to other intralesional corticosteroids. Other modalities with varying cutaneous findings (Figures 1 and 2). reports of success include systemic corticosteroids, cyclos­ porine, mycophenolate mofetil, oral tetracyclines, oral reti­ Linear Hyperpigmentation noids, thalidomide, and hydroxychloroquine, although Following Blaschko’s Lines Without relapses after discontinuation of treatment have been reported.10 Systemic Findings We describe the most common dermatological disorders Linear Atrophoderma of Moulin that may present with linear hyperpigmentation following Linear atrophoderma of Moulin (LAM) is an acquired Blaschko’s lines without associated systemic findings dermatological disease primarily affecting children and (Table 1). adolescents. It appears as unilateral round or oval hyper­ pigmented macules and atrophic band-like skin lesions Blaschkoid Lichen Planus following Blaschko’s lines over the trunk or limbs. Blaschkoid lichen planus (LP) is rare, manifesting as Truncal lesions typically form an S-shaped pattern.11,12 It hyperpigmented inflammatory macules and patches is typically a non-inflammatory disease although an arranged in a linear, S-shaped, or whorled pattern follow­ inflammatory phase was reported. While most patients ing Blaschko’s lines (blaschkitis), without koebnerization. develop non-sclerotic hyperpigmentation only, atypical It differs from linear LP and accounts for approximately presentations can present with bilateral telangiectasias, 3 0.5% of LP cases (Figure 3). Mostly, it present as an leukonychia, and lentiginous skin melanoma.12 isolated finding. However, Sil et al recently reported blas­ There is no proven effective treatment for LAM, and chkoid LP in the setting of concurrent childhood-onset both topical steroids and high-dose penicillin have been 4 systemic lupus erythematosus. reported to be ineffective. Few cases have shown stabili­ zation of lesions with oral potassium aminobenzoate 12 g/ Lichen Planus Pigmentosus day. Other studies have reported partial responses to topi­ Lichen planus pigmentosus (LPP) is another rare form of cal calcipotriol and intralesional platelet-rich plasma ther­ LP that mostly affects adults with skin phototypes III–V. It apy, while Zaouak et al reported a case successfully treated presents as dark brown macules and patches that follow with methotrexate.13–15 Blaschko’s lines and predominately affects sun-exposed areas (especially the forehead, temples, and neck) and Lichen Striatus and Blaschkitis flexor folds. Patients with this condition are usually Lichen striatus (LS) and blaschkitis are inflammatory con­ asymptomatic, but some patients report mild pruritus or ditions following Blaschko lines. LS is primarily affecting burning sensation. Unlike classical LP, the palms, soles, children, while blaschkitis is mainly affecting adults. They 5 nails, and oral mucosa are not involved. In one uncon­ can be differentiated from other diseases in this category trolled study, lightening of the pigmentation occurred in by being inflammatory rather than pigmentary. In dark- 54% (7/13) patients treated with topical tacrolimus for skinned individuals, LS may present as a hypopigmented 6–8 12–16 weeks. lesion. In blaschkitis, it commonly presents as inflamma­ tory papules and vesicles on adults trunk.16 Linear Lichen Planopilaris Lichen planopilaris (LPP) is a primary diffuse, scaly patch, Other Rare Conditions or plaque associated with cicatricial alopecia that rarely There are other few conditions that may present as linear presents in a linear distribution. It may present as a linear hyperpigmentation following Blaschko’s lines without sys­ patch or plaque associated with scaling alopecia, followed temic findings. They include progressive cribriform and by scarring over the scalp or face. It is characterized by zosteriform hyperpigmentation (PCZH), unilateral nevoid lymphocytic inflammation directed toward the infundibu­ acanthosis nigricans (UNAN), and linear macular amyloi­ lum and isthmus portions of the hair follicle, leading to dosis (LMA). PCZH is a rare condition that presents at follicular scarring and irreversible hair loss.9,10 birth with Blaschkoid hyperpigmented lesions with no 24 submit your manuscript | www.dovepress.com Clinical, Cosmetic and Inv estigational Dermatology 2021:14 DovePress Dovepress Alkhowailed et al Figure 1 Clinical approach for linear hyperpigmentation. Abbreviations: XL-HED, X-linked reticulate pigmentary disorder; CALM, café au lait macule; MAS, McCune–Albright syndrome; LWNH, linear whorled nevoid hypermelanosis; FDH, focal dermal hypoplasia; XLRPD, X-linked reticulate pigmentary disorder; CHHS, Conradi–Hünermann–Happle syndrome. systemic symptoms.17 UNAN is a rare variant of acantho­ Blaschko’s lines, and their associated systemic findings sis nigricans that usually tend to be unilateral and follow­ (Table 2). ing lines of Blascko without any internal involvement.18 Macular amyloidosis is a depositional disease caused by Focal Dermal Hypoplasia amyloid deposition in the dermis. In a minority of cases,