Case Report Open Access
Facial Blaschko-Linear Cutaneous Lupus Erythematosus in Childhood: A Case and Review
Chii-Shyan Wang1, Yu-Hung Wu2,3, Hsuan-Hsiang Chen4*
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
  1. Bansal C, Ross AS, Cusack CA. Chronic cutaneous lupus in childhood: a report of two cases and review of the literature. Int J Dermatol. 2008;47(5):525-526. doi: 10.1111/j.1365-4632.2008.03402.x.
  2. Umbert P, Winkelman RK. Concurrent localized scleroderma and discoid lupus erythematosus. Cutaneous mixed or overlap syndrome. Arch Dermatol. 1978;114(10):1473-1478.
  3. Abe M, Ishikawa O, Miyachi Y. Linear cutaneous lupus erythematosus following the lines of Blaschko. Br J Dermatol. 1998;139:307–310. doi:10.1590/abd1806-4841.20163800
  4. Frances L, Betlloch I, Leiva-Salinas M, Marin I, Pascual JC. Subacute cutaneous lupus erythematosus starting as linear lupus erythematosus. Int J Dermatol. 2016;55:173-176. doi: 10.1111/ijd.12829. Epub 2015 Jul 31.
  5. Kim J, Lee SH, Roh MR. Linear cutaneous lupus erythematosus on the midline of the face.J Dermatol.2010;38(6):309-312.doi: 10.1111/j.1346-8138.2010.01013.x
  6. Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Linear cutaneous lupus erythematosus in the lines of Blaschko. Pediatr Dermatol. 2001;18(5):396-399. DOI:10.1046/j.1525-1470.2001.01963.x
  7. Green JJ, Baker DJ. Linear childhood discoid lupus erythematosus following the lines of Blaschko: a case report with review of the linear manifestations of lupus erythematosus. Pediatr Dermatol. 1999;16(2):128-133.
  8. Davies MG, Newman P. Linear cutaneous lupus erythematosus in association with ipsilateral submandibular myoepithelial sialadenitis. Clin Exp Dermatol. 2001;26(1):56-58.
  9. Choi JC, Chang SE, Choi JH, Sung KJ,Moon KC,Koh JK. A linear erythema on the nose of a korean girl. J Dermatol. 2001;28(2):106-107.
  10. Requena C, Torrelo A, de Prada I, Zambrano A. Linear childhood cutaneous lupus erythematosus following Blaschko lines. J Eur Acad Dermatol Venereol. 2002;16(6):618-620.
  11. Imhof L, Kerl K, Barysch MJ, Dummer R,French LE,Hofbauer GF. Facial blaschkitis:case and review.Dermatology.2011;223(1):1-3. doi: 10.1159/000328136
  12. Kawachi Y, Taguchi S, Fujisawa Y, Furuta J,Nakamura Y,Ishii Y, et al. Linear childhood discoid lupus erythematosus following the lines of Blaschko: successfully treated with topical tacrolimus. Pediatr Dermatol. 2011;28(2):205-207. doi: 10.1111/j.1525-1470.2010.01249.x
  13. Jin H, Zhang G, Zhou Y, Chang C, Lu Q. Old lines tell new tales: Blaschko linear lupus erythematosus. Autoimmun Rev. 2016;15(4):291-306. doi: 10.1016/j.autrev.2015.11.014
  14. Ma H, Liao M, Qiu S, Lu R, Lu C. Linear cutaneous lupus erythematosus with calcinosis cutis and milia. Pediatr Dermatol. 2015;32(1):e33-35. doi: 10.1111/pde.12496.
  15. Nagai Y, Ishikawa O, Hattori T, Ogawa T. Linear lupus erythematosus profundus on the scalp following the lines of Blaschko. Eur J Dermatol. 2003;13(3):294-296.
  16. Tamiya H, Sowa J, Nakanishi T, Adachi M,Ishii M,Kobayashi H. Linear lupus erythematosus profundus on the face, following the lines of Blaschko. Int J Dermatol. 2010;49(12):1459-1461. doi: 10.1111/j.1365-4632.2009.04285.x.
  17. Tada J, Arata J, Katayama H. Linear lupus erythematosus profundus in a child. J Am Acad Dermatol. 1991;24(5 Pt 2):871-874.
  18. Innocenzi D, Pranteda G, Giombini S, Vitaliano Silipo, Ugo Bottoni, Stefano Calvieri. Linear lupus erythematosus profundus in an adolescent. Eur J Dermatol. 1997;7:445-447.
  19. Tamada Y, Arisawa S, Ikeya T, Yokoi T,Hara K,Matsumoto Y. Linear lupus erythematosus profundus in a young man. Br J Dermatol. 1999;140(1):177-178.
  20. Marzano AV, Tanzi C, Caputo R, Alessi E. Sclerodermic linear lupus panniculitis: report of two cases. Dermatology. 2005;210(4):329-332.
  21. Happle R, Assim A. The lines of Blaschko on the head and neck. J Am Acad Dermatol 2001;44(4):612-615.
  22. Bolognia JL, Jorizzo JL, Rapini RP: Blaschko’s lines on the face; in Bolognia JL, Jorizzo JL, Rapini RP (eds): Dermatology. St. Louis, Mosby. 2007;1:842. (Bouzit N, Grezard P, Wolf F, Balme B, Perrot H. Linear cutaneous lupus erythematosus in an adult. Dermatology. 1999; 199(1):60-62.)
  23. Happle R. Mosaicism in human skin. Arch Dermatol. 1993;129(11):1460-1470.
  24. Engelmann DE, Kotz EA, Maize JC. Linear cutaneous lupus erythematosus in the lines of Blaschko. Pediatr Dermatol. 2007;24(2):125-129.
  25. Seitz CS, Breocker EB, Trautmann A. Linear variant of chronic cutaneous lupus erythematosus: a clue for the pathogenesis of chronic cutaneous lupus erythematosus? Lupus 2008;17(12):1136-1139. doi: 10.1177/0961203308092425.
  26. Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Linear eruptions of the nose in childhood: a form of lichen striatus? Br J Dermatol. 2000;142(6):1208-1212.
 
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