Facial Blaschko-Linear Cutaneous Lupus Erythematosus in Childhood: A Case and Review

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Case Report Open Access

Chii-Shyan Wang¹, Yu-Hung Wu^2,3, Hsuan-Hsiang Chen^4*

¹Department of Dermatology, En Chu Kong Hospital, New Taipei City, Taiwan
²Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
³Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan
⁴Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

*Corresponding author: Hsuan-Hsiang Chen, MD, Department of Dermatology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei, Taiwan, Tel: +886-2-2356-2141; Fax: +886-2-2393-4177;E-mail:

Received: December 13, 2016; Accepted: December 25, 2016; Published: December 30, 2016

Citation: Wang CS, Wu YH, Chen HH (2016) Facial Blaschko-Linear Cutaneous Lupus Erythematosus in Childhood: A Case and Review. Clin Res Dermatol Open Access 3(6): 1-5.

Abstract

We report on a 5-year-old girl with a pruritic, erythematous cutaneous eruption on the right side of the face for more than 1 year. The lesion had a linear distribution following the lines of Blaschko. Histopathological findings and direct immunofluorescence were compatible with cutaneous lupus erythematosus. We consider this unusual clinical presentation of childhood facial "Blaschko-linear cutaneous lupus erythematosus" to be a distinct subtype of lupus erythematosus. The clinical characteristics and a review of the literature are presented.

Keywords: lines, Linear; Lupus Erythematosus; Facial; Childhood;

Case Report

A 5-year-old girl went to our clinic presented with a more than 1 year history of linear and annular erythematous patches and telangiectasia from right cheek to right forehead (Figure1a), which was consistent with the implemented lines of Blaschko on the head (Figure1b). Some mild atrophic center over right forehead was noted (Figure1c). She was treated with topical steroids by other dermatologists for more than 1 year but in vain. There were no oral ulcer, alopecia, muscular weakness, or arthralgia, but photosensitivity was noted. The clinical impression was Discoid Lupus Erythematosus (DLE). The initial screening laboratory examination results revealed negative Antinuclear Antibodies (ANA), and positive anti-ENA antibodies. The complement C3, C4, and complete blood count were all within normal limits. The further laboratory examination confirmed positive anti-nDNA antibodies (45.3 IU/ml, >10 IU/ml), and negative anti-Sm/RNP, anti-SSA or anti-SSB antibodies. A skin biopsy was performed on the right forehead and the sample was sent for histological and Direct Immuno fluorescent Examination (DIF). Microscopic features showed papillary dermal edema and perivascular and periappendageal infiltration in both superficial and deep dermis. There were increased dermal mucin deposition and perivascular lymphocytic infiltration (Figure 2). The higher magnification showed interface dermatitis in the epidermis characterized by presence of basal cell vacuolar change, lymphocyte exocytosis, and dyskeratotic cells (Figure 3). Pigment incontinence was present in the papillary dermis. The DIF of the skin biopsy demonstrated a thick linear-granular IgG deposition in the basement membrane zone (Figure 4). There were also granular IgA, IgM, and C3 deposition at the dermo-epidermal junction. These findings were consistent with cutaneous lupus erythematosus. The systemic workup revealed normal chest x ray, and urianalysis. The repeated laboratory workup showed complete blood count, renal profile, total protein and albumin were within normal limits. The ANA, anti-dsDNA antibody, anticardiolipin IgM antibody, C3, C4, and direct Coombs test were all negative. Oral hydroxychloroquine 100mg a day was then prescribed. The skin lesions improved after treatment.

Discussion

The clinical presentation of childhood DLE is similar to that of the adult form. Over 50% of patients presented with lesions before the age of 10 years. The remainder presented between the ages of 10 and 16 years [1]. Unlike adults with a female predominance, it seems that there is no sex association in children. Some authors

Figure 1a: Linear and annular erythematous patches and telangiectasia from right cheek to right forehead.

Figure 1b: Schema of the lines of Blaschko on the face (adapted from Happle et al. [21]) and the distribution of the eruption in our case (red dots).

Figure 1c: Some mild atrophic center over right forehead.

Figure 2: Scanning magnification showed papillary dermal edema and perivascular and periappendageal infiltration in both superficial and deep dermis. There were increased dermal mucin deposition and perivascular lymphocytic infiltration. (H & E, original magnification ×100)

Figure 3: The higher magnification showed interface dermatitis in the epidermis characterized by presence of basal cell vacuolar change, lymphocyte exocytosis, and dyskeratotic cells. Pigment incontinence was present in the papillary dermis. (H & E, original magnification ×400)

Figure 4: The direct immunofluorescence of IgG demonstrated a thick linear-granular deposition in the basement membrane zone. (original magnification x400)

suggest a higher frequency of transition from DLE to systemic lupus erythematosus (SLE). The rate of transformation is 25%, higher than the rate observed in adults (approximately 6%) [1]. Therefore, repeated laboratory studies are essential in children diagnosed with DLE. Unfortunately, neither the serology on presentation nor the clinical presentation is predictive of future systemic involvement.

The linear distribution of our patient is different from the typical DLE lesions. Linear Cutaneous Lupus Erythematosus (LCLE) was first described in 1978 [2]. It is a term proposed for DLE with a linear configuration [3]. This unusual presentation of lupus erythematosus is mostly seen in children and young adults. Till now, fewer than 30 cases in both adults and children have been published [4, 5]. Among them, only 15 cases of childhood diagnosed as facial LCLE have been reported (Table 1) [3, 6-16]. Nearly half of the cases presented with lesions before the age of 7 years. There seems to be a female predominance in children LCLE, although the female predominance is not as significant as in SLE patients. The typical clinical manifestations are single or multiple erythematous, atrophic, hyperkeratotic, dyschromic linear or annular plaques, patches, or even localized non-scarring alopecia distributed along the lines of the head and neck. The lesions are usually asymptomatic, with a low incidence of photosensitivity. This unique presentation can be considered as DLE following the lines of Blaschko, but other types of lupus with a linear distribution, such as Lupus Erythematosus Profundus (LEP), have also been described in some pediatric patients [15- 20]. Most reported findings in DIF are variable and DIF was not performed in nearly half of the cases. Serological analysis of these patients reveals that some autoantibodies (especially ANA) could be found in few cases, which suggests that the linear lesions might have the potential of triggering systemic autoimmune reaction. We noticed a low rate of progression to systemic disease in this group. However, the follow-up time of most cases in this group is not long enough. It has not been conclusively proven that weather these cases would eventually progress to SLE. A regular long-term follow up is still mandatory.

lines of the face and neck region form an unique arch shape from the oral angle to the orbital region on the face (Figure1c) [21, 22]. Blaschko-linear lesions probably reflect a mosaic condition from post-zygomatic somatic mutation or

Table 1: Cases of facial linear cutaneous lupus erythematosus (LCLE) in children reported in the literature.

References	Age at onset, Years/sex	Types of LCLE	Facial localization	Laboratory exam	DIF	Systemic involvement	Treatment
Abe et al. [3]	3/female	CDLE	Right cheek	ANA: 1:80 homogeneous speckled	IgM, C3 at the BMZ	No	Oral: dapsone
Abe et al. [3]	11/female	CDLE	Left side of chin and neck	Unremarkable	Negative	No	Oral: dapsone, Topical: 5% ibuprofenpiconol ointment
Lee et al. [6]	4/male	CDLE	Left upper cheek, perioral area	Unremarkable	IgM at DEJ	No	Oral: hydroxychloroquine
Green and Baker [7]	7/male	CDLE	Cheeks, NLFs, occiput, parietal scalp	ANA: 1:80 (+) speckled	NP	No	Topical: 0.05% aclometasone diproprinate, 0.2% hydrocortisone valerate
Davies and Newman [8]	12/female	CDLE	Left cheek	Unremarkable	NP	No	Oral: Dapsone Topical: corticosteroids
Choi et al. [9]	6/female	CDLE	Nose	Unremarkable	NP	No	Oral: hydroxychloroquine
Requena et al.[10]	3/male	CDLE	Right side of chin and neck	Unremarkable	NP	No	Topical: Corticosteroids
Imhof et al. [11]	15/ female	CDLE	Right upper cheek, perioral area	Unremarkable	IgM, IgG, C3 at DEJ	No	Oral: hydroxychloroquine, isotretinoin Topical: pimecrolimus Light: intense pulsed light
Kawachi et al. [12]	4/female	CDLE	Right side of cheek, auricle, neck	Unremarkable	IgM, C3 along DEJ	No	Topical: 0.03% tacrolimus ointment
Jin et al. [13]	9/male	CDLE	Forehead, left check, preauricular region	Unremarkable	IgG, IgA, IgM, C3 along DEJ	No	Oral: hydroxychloroquine Topical: 0.03% tacrolimus ointment
Jin et al. [13]	12/female	LCLE	Right corner of mouth to right side of neck	Unremarkable	NP	No	Oral: hydroxychloroquine Topical: 0.03% tacrolimus ointment
Jin et al. [13]	12/male	LCLE	Right side of forehead, nose, cheek, eye, right corner of mouth to neck	ANA: 1:320 (+), C3: 0.70 g/L, C4: 0.14 g/L	Negative	No	Oral: hydroxychloroquine, glycyrrhizin Topical: 0.03% tacrolimus ointment
Ma et al. [14]	6/male	LCLE	Left mandible, submandibular triangle, anterior auricle	Unremarkable	NP	No	Topical: corticosteroids, 0.1% tacrolimus ointment
Nagai et al. [15]	10/female	LEP	Left side of forehead temporal area	ANA: 1:320 (+) homogenous speckled	NP	No	Topical: corticosteroids
Tamiya et al. [16]	6/female	LEP	Left forehead to the left glabella, nose	Unremarkable	IgM (+)	No	Oral: Prednisolone Topical: prednisolone valerate acetate ointment
Present case	4/female	CDLE	Right cheek and scalp	anti-nDNA antibodies	IgG, IgM, IgA, C3 at DEJ	No	Oral: hydroxychloroquine

LCLE, linear cutaneous lupus erythematosus; CDLE, chronic discoid lupus erythematosus; LEP, lupus erythematosus profundus, ANA, antinuclearantibodies; NP, not performed; DIF, direct immunofluorescent examination; BMZ, basement membrane zone; DEJ, dermo-epidermal junction

lyonization (the inactivation of an X chromosome) [23]. The presence of mosaic genetically abnormal skin cells (such as keratinocytes, fibroblasts, or vascular endothelial cells), rather than circulating immune cells, might be responsible for the presence of lines distributed skin lesions in LCLE patients. Thus, cutaneous antigenic mosaicism, e.g. induced by a viral infection or other trigger factors, could trigger a strictly localized T cell response. This hypothesis could explain blaschko linear lesions to other cutaneous autoimmune diseases as well. In Blaschko-LCLE, exogenic influences might lead to the expression of new autoantigens followed by loss of immune tolerance to the abnormal epithelial cell clones. The subsequent T-cell-mediated reaction against the abnormal keratinocytes or other cutaneous cells that follow lines causes clinical visualization of the line [24]. Seitz et al. [25] suggested that LCLE can be explained by the presence of genetically variant keratinocytes that lack a protective factor against ultraviolet-induced damage and show aberrant cytokine expression or major histocompatibility complex expression. Our patient did not have the usual trigger factors like infections, drugs, pesticides, or heavy metals, but the history of photosensitivity from sunlight and ultraviolet radiation may explain the early onset of this unique disease.

The differential diagnosis of Blaschko-LCLE includes other acquired inflammatory diseases distributed along Blaschko's lines, such as lichen striatus, linear lichen planus, linear morphea, linear granuloma annulare, or linear psoriasis, etc. Skin biopsy is helpful but often not sufficient to make the correct diagnosis. It may be impossible to differentiate lichen striatus from LCLE [26]. Histologically, these two conditions share many common features. It is necessary to perform DIF to differentiate equivocal cases. Physicians should also take into account clinical presentation, histological evaluation and response to treatment before making a diagnosis of Blaschko-LCLE.

Previously reported therapies for facial LCLE of childhood include topical steroids [7, 8, 10, 14-16], pimecrolimus [11], tarcrolimus [12-14], oral steroids [16], dapsone [3, 8], hydroxychloroquine [6, 9, 11, 13], isotretinoin [11], and intense pulsed light [11]. However, patients show various responses to these therapies. Our patient improved after oral hydroxychloroquine and is still followed up regularly.

In conclusion, Blaschko-LCLE is a distinct subtype of lupus erythematosus, often occurring in children. Its typical clinical manifestation is Blaschko-linear distributed skin lesions with cutaneous manifestations of DLE or LEP. Photosensitivity and serological autoantibodies are often absent, with minimal possibility of progression to SLE. Blaschko-LCLE patients provide a promising model for studying underlying immunological and molecular mechanisms of cutaneous mosaicism.

References