
	Version PDF

Subacute cutaneous lupus erythematosus on the lines of Blaschko

European Journal of Dermatology. Volume 16, Number 3, 302-6, May-June 2006, Clinical report

Summary

Author(s) : Heike Röckmann, Gabriele Feller, Dirk Schadendorf, Sergij Goerdt , Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany, Skin Cancer Unit of the German Cancer Research Center at the Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany.

Summary : We describe a 42-year-old woman who had erythemateous plaques with sharply demarcated margins and fine scaling on her right trunk and leg. The lesions had a linear distribution following the lines of Blaschko. Histological findings supported the diagnosis of subacute cutaneous lupus erythematosus (SCLE) on the lines of Blaschko. Treatment with systemic corticosteroids and anti-malarial agents resulted in remission. Up to now, eighteen cases of linear lupus erythematosus have been described. Linear lupus erythematosus mostly affects children presenting with lesions on the scalp that were classified as discoid lupus erythematosus. To our knowledge, this is the first case of subacute cutaneous lupus erythematosus on the lines of Blaschko.

Keywords : subacute cutaneous lupus erythematodes, lines of Blaschko, CDLE, mosaicism

Pictures

ARTICLE

Auteur(s) : Heike Röckmann^1,2, Gabriele Feller¹, Dirk Schadendorf^1,2, Sergij Goerdt¹

¹Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany
²Skin Cancer Unit of the German Cancer Research Center at the Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany

accepté le 21 Decembre 2005

Linear configurations of cutaneous lupus erythematodes or discoid lupus erythematodes have rarely been described. Blaschko lines are usually used to describe the linear distribution of various nevoid diseases and acquired skin diseases such as lichen striatus, lichen planus and morphea. We report a woman with subacute cutaneous lupus erythematodes displaying a Blaschko-linear pattern.

Case report

A 42-year-old woman presented with a 7-week history of increasing scaly erythema followed by the development of patches and plaques on the right side of her trunk and chest in a linear distribution. The lesions then spread downwards to her right leg and foot. She complained about severe itching, but she was otherwise healthy. She had no history of a preceding trauma, infection or sun exposure, and no family history of any autoimmune disease.

On examination, an erythemateous band from the medial aspect of the foot to her right groin and hip was seen (figures 1A-C). Three short parallel bands were seen on her right back and gluteal region (figure 1D). Besides, there was an S-shaped erythemateous papular squamous line on the right side of her chest (figure 1C). In detail, the psoriasiform papulosquamous lesions showed an annular or semi-annular configuration with inverted scales (figure 2).

Routine laboratory blood tests revealed normal values. Antinuclear antibodies (ANA) were positive (1: 2560) tested by indirect immunofluourescence on HEPII cells and liver tissue as control. Atypical ANCA (> 1: 16), not allowing a distinction between c- and p-ANCA, and anti-SS-A/Ro antibodies (ELISA) were also found. No auto-antibodies were detected against Sm, SSB/La, U1-sn-RNP-Sm, Scl-70 and double stranded DNA.

Skin biopsies from the trunk, the gluteal region and the lower leg were taken from the margin of an erythemateous patch. Histological examination revealed an atrophic epidermis and follicular hyperkeratosis. Dense mononuclear cell infiltrate around dermal blood vessels and appendages as well as hydropic degeneration of the epidermal basal cell layer was observed (figures 3A-C). Direct immunofluourescence (DIF) was negative.

For analysis of photosensitivity UVA testing (320-460 nm; 6-15 J/ cm²) as well as UVB testing (285-350 nm; 20-50 mJ/m²) was carried out. We additionally performed a repetitive UVA testing (320-400 nm) with 5, 10 and 30 J/cm² with reading times at 24, 48, 72 hours and 5 days. The patient exhibited photosensitivity beginning after 48 h in repetitive UVA field with the occurrence of erythemateous papules. No reactivity could be elicited after UVA or UVB testing as described above.

Further extensive examinations regarding systemic involvement of the disease did not show any abnormalities. Based on clinical, laboratory and histological findings we made a diagnosis of subacute cutaneous lupus erythematosus on the lines of Blaschko.

Treatment with systemic corticosteroids and chloroquine (250 mg/d) resulted in significant improvement of the lesions. The initial dose of 60 mg/d methylprednisolone orally was reduced after 3 weeks and finished after four months. The local therapy was restricted to urea with a maintenance therapy of chloroquine.

Discussion

Blaschko-linear variants of LE have been described only rarely. Umbert and Winkelmann first reported a linear variant of cutaneous LE in 1978 as cutaneous “mixed/overlap syndrome” with linear scleroderma and discoid lupus erythematodes [1]. Since then 18 patients have been described. We have summarized all published cases, including the present case, in (Table 1).

In 1981 subacute cutaneous lupus erythematosus was first recognized by Gilliam and Sontheimer as a unique subset of lupus erythematosus (LE) that consists of an erythematous nonscarring papulosquamous eruption in a photodistribution [2]. The widespread subphenotype was in the following years analysed by many investigators and the clinical relevance with respect to management and prognosis could be evidenced (overview in Sontheimer [3]).

Recently 4 of 18 cases (22%) were diagnosed as linear lupus erythematosus profundus (LEP) [4-7], while 9 cases (50%) were specified as a linear variant of cutaneous discoid lupus erythematosus (CDLE) [1, 8-11] and one case (6%) was a bullous systemic LE [12]. Three cases were described as cutaneous LE without further differentiation [13-15]. Hitherto, a linear variant of subacute cutaneous LE (SCLE) has not been described unequivocally.

With respect to the three cases of linear LE that were not further specified [13-15], Heid et al. [13] described a 35-year-old male patient who presented with a unilateral skin eruption with Blaschko-linear extension. In this case, the patient was positive for anti-RNP type anti-nuclear antibodies, and direct immunofluourescence was positive in biopsies of both the lesions and the healthy skin. In view of the positive DIF and antibodies as well as a high titer of ANA (1:1280), a diagnosis of SCLE in this particular case was possible. In the cases described by Lee et al. [14] and Davies et al. [15], the clinical features, negative ANA and positive lesional DIF, may be interpreted in favour of a CDLE. Interestingly, the case presented by Davies et al. described an 18-year-old patient with an 8-year history of a left-sided submandibular mass associated with a linear erythemateous scaly lesion in the overlying skin. The cutaneous LE improved significantly after removal of the mass that was diagnosed histopathologically as inflammation of the submandibular salivary gland. The local and temporal co-occurrence of the two conditions indicated a causal relationship.

In general, linear LE and the non-linear forms of LE differ in several aspects. The mean age of all published linear LE cases is 16.8 years with a range from 3 to 48 years. At the onset of the disease 11 of 18 patients were under the age of 15 years, while only 3 patients were over 30 years old. In contrast, non-linear cutaneous LE develops usually between the ages of 20 and 40 [16]. In addition, the overall incidence of LE in childhood is extremely rare. Fewer than 2% of patients with CDLE develop this disease before the age of 10 [17].

Furthermore, LE in children is characterized by a high frequency of progression into systemic disease [17], while the linear variants do not show progression to SLE neither in young nor in adult patients. On the other hand Roholt et al. [12] described a 9-year-old girl who developed linear bullous skin lesions after she had been diagnosed with SLE eight weeks earlier.

In previous cases of linear LE no photosensitivity was reported. However, this has to be interpreted with caution since only anamnestic information was used. Also in our case anamnestic information indicated no photosensitivity, but the actual test did reveal a photosensitivity. Nevertheless, the unanimous reports of prior cases indicate that light is not a primary trigger, and the sensitivity in our patient may be SCLE specific or accidental.

The origin of Blaschko’s lines remains a matter of debate. In 1901 Blaschko described acquired naevoid skin diseases following constant lines [18]. They did not correspond to other cutaneous lines such as dermatomes. In practical terms, it is most important to distinguish Blaschko’s lines and dermatomes. The differences are most apparent on the trunk, where Blaschko’s lines manifest as arcs on the upper chest, S-shaped lines on the abdomen and V-shaped lines as the lesions approach the posterior midline. The linear lesions as seen in our patient fully feature the characteristic of Blaschko’s lines (figure 4). Dermatoses on the lines of Blaschko are separated into congenital X-linked, naevoid as well as acquired disorders [19]. The differential diagnosis of inflammatory acquired blaschko-linear lesions comprises a variety of entities, such as lichen striatus (“Blaschkitis”), cutaneous LE, psoriasis, lichen niditus, lichen planus, mycosis fungoides, fixed drug eruption and linear contact dermatitis [19-23]. The differentiation of these linear inflammatory lesions may sometimes be difficult.

One explanation for the occurrence of the lines of Blaschko is that they correspond to the direction of migration and clonal expansion of cells during cutaneous embryogenesis [19]. The cutaneous lesions that follow the lines of Blaschko seem to reflect a mosaic condition due to postzygotic somatic mutation. The cause of the acquired Blaschko-linear lesions in specific diseases may lead to the unmasking of tolerance to an abnormal keratinocyte clone (or other dermal cells) that remained hidden in these cells [15, 24, 25]. In Blaschko-linear LE, exogenic influences might lead to the expression of new auto-antigens followed by a loss of immune tolerance to the abnormal epithelial cell clones. The subsequent T-cell mediated reaction against the abnormal keratinocytes that follow the lines of Blaschko causes clinical visualization of the line as lupus erythematosus. The eruption of the disease could be triggered by trauma or irritation or other exogenous agents with a presumptive role in LE development including ultraviolet light, drugs, pesticides, heavy metals and other elements [26].

In summary, Blaschko-linear skin lesions are a hallmark of some acquired dermatoses such as lichen striatus. The frequency of cases of lupus erythematosus following the lines of Blaschko is low. Patients with linear LE are mostly specified as discoid lupus erythematosus at a younger age. Linear LE shows a lack of female predominance, a low incidence of photosensitivity and a less frequent progression to systemic lupus erythematosus. The case presented here describes the first patient with subacute cutaneous lupus erythematosus following the lines of Blaschko.
Table 1 Cases of linear lupus erythematosus on the lines of Blaschko in the literature

Case	Age	Sex	Location	Diagnose	ANA	DIF	Reference
1.	7	F	hand/ forearm	CDLE	-	+	Umbert et al. [1]
2.	48	M	face	CDLE	-	-	Richarz et al. [27]
3.	3	M	leg	LEP	-	-	Tada et al. [5]
4.	9	F	hand/forearm	SLE	1: 1024	+	Roholtet al. [12]
5.	35	M	arm, chest	NS	1:1280; + RNP	+	Heid et al. [13]
6.	14	M	arm, breast	LEP	1 : 40	+	Innocenzi et al. [7]
7.	3	F	face	CDLE	-	+	Abe et al. [8]
8.	11	F	face, neck	CDLE	-	-	Abe et al. [8]
9.	18	M	arm	LEP	-	+	Tamada et al. [6]
10.	8	M	face, trunk	CDLE	-	ND	Green et al. [9]
11.	29	F	face	CDLE	-	+	Bouzit et al. [10]
12.	23	M	face	CDLE	-	+	Abe et al., [28]
13.	12	F	face	CDLE	-	ND	Davies et al. [15]
14.	4	M	face	CLE	-	+	Lee et al. [14]
15.	3	M	face, neck	CDLE	-	ND	Requena et al. [11]
16.	24	M	arm, trunk	TLE	-	-	Pacheco et al. [29]
17.	10	F	face, scalp	LEP	1: 320	ND	Nagai et al. [4]
Present case	42	F	leg, trunk	SCLE	1:2560, + Ro-SSA	-

References

1 Umbert P, Winkelmann RK. Concurrent localized scleroderma and discoid lupus erythematosus. Cutaneous ’mixed’ or ’overlap’ syndrome. Arch Dermatol 1978; 114: 1473-8.

2 Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981; 4: 471-5.

3 Sontheimer RD. Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus erythematosus defined by characteristic cutaneous, pathological, immunological, and genetic findings. Autoimmun Rev 2005; 4: 253-63.

4 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: 294-6.

5 Tada J, Arata J, Katayama H. Linear lupus erythematosus profundus in a child. J Am Acad Dermatol 1991; 24: 871-4.

6 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: 177-8.

7 Innocenzi D, Pranteda G, Giombini S, Silipo V, Bottoni U, Calvieri S. Linear lupus erythematosus profundus following the lines of Blaschko. Eur J Dermatol 1997; 7: 445-7.

8 Abe M, Ishikawa O, Miyachi Y. Linear cutaneous lupus erythematosus following the lines of Blaschko. Br J Dermatol 1998; 139: 307-10.

9 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: 128-33.

10 Bouzit N, Grezard P, Wolf F, Balme B, Perrot H. Linear cutaneous lupus erythematosus in an adult. Dermatology 1999; 199: 60-2.

11 Requena C, Torrelo A, de Prada I, Zambrano A. Linear childhood cutaneous lupus erythematosus following Blaschko lines. J Eur Acad Dermatol Venereol 2002; 16: 618-20.

12 Roholt NS, Lapiere JC, Wang JI, Bernstein LJ, Woodley DT, Eramo LR. Localized linear bullous eruption of systemic lupus erythematosus in a child. Pediatr Dermatol 1995; 12: 138-44.

13 Heid E, Grosshans E, Gonda J, Pare M, Lipsker D. Blaschkolinear eruption with biological signs of lupus. Ann Dermatol Venereol 1996; 123: 331-3.

14 Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Linear cutaneous lupus erythematosus in the lines of Blaschko. Pediatr Dermatol 2001; 18: 396-9.

15 Davies MG, Newman P. Linear cutaneous lupus erythematodes in association with ipsilateral submandibular myoepithelial sialadenitis. Clin Exp Dermatol 2001; 26: 56-8.

16 Tebbe B. Clinical course and prognosis of cutaneous lupus erythematosus. Clin Dermatol 2004; 22: 121-4.

17 George PM, Tunnessen Jr. WW. Childhood discoid lupus erythematosus. Arch Dermatol 1993; 129: 613-7.

18 Blaschko A. Die Nervenverteilung der Haut in ihrer Beziehung zu den Erkrankungen der Haut. Braunmüller: Wien und Leipzig, 1901.

19 Bolognia JL, Orlow SJ, Glick SA. Lines of Blaschko. J Am Acad Dermatol 1994; 31: 157-90; (quiz 190-2).

20 Schadendorf D, Haas N, Nürnberger F, Czarnetzki BM. Histologische, immunhistochemische und elektronenmikroskopische Charakterisierung eines ILVEN. Dermatol Monatschr 1993; 179: 18-21.

21 Grosshans EM. Acquired blaschkolinear dermatoses. Am J Med Genet 1999; 85: 334-7.

22 Atherton DJ, Kahana M, Russell-Jones R. Naevoid psoriasis. Br J Dermatol 1989; 120: 837-41.

23 Sigal-Nahum M, Konqui A, Gaulier A, Sigal S. Linear fixed drug eruption. Br J Dermatol 1988; 118: 849-51.

24 Happle R. Transposable elements and the lines of Blaschko: a new perspective. Dermatology 2002; 204: 4-7.

25 Happle R. Muster auf der Haut. Neues zu entwicklungsbiologischen und genetischen Ursachen. Hautarzt 2004; 55: 960-8.

26 Shapiro M, Sosis AC, Junkins-Hopkins JM, Werth VP. Lupus erythematosus induced by medications, ultraviolet radiation, and other exogenous agents: a review, with special focus on the development of subacute cutaneous lupus erythematosus in a genetically predisposed individual. Int J Dermatol 2004; 43: 87-94.

27 Richarz U, Hübner J, Schmeel A, Bauer R. Striärer Lupus erythematodes im Verlauf der Blaschko-Linien. Hautarzt 1986; 37: 335-7.

28 Abe M, Ohnishi K, Ishikawa O. Guess what? Linear cutaneous lupus erythematous (LCLE): relationship with Blaschko’s lines. Eur J Dermatol 2000; 10: 229-31.

29 Pacheco TR, Spates ST, Lee LA. Unilateral tumid lupus erythematosus. Lupus 2002; 11: 388-91.