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A Case of Lichen Sclerosus of the Scalp Associated With Autoantibodies to Extracellular Matrix Protein 1

A Case of Lichen Sclerosus of the Scalp Associated With Autoantibodies to Extracellular Matrix... Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown cause with a predilection for the anogenital area. Recent investigation has identified serum IgG autoantibodies specific to extracellular matrix protein 1 (ECM1) in 74% of patients with anogenital LS1; however, the rationale for humoral autoimmunity to ECM1 in the extragenital disease has been enigmatic. Herein, we describe the first case to our knowledge of extragenital LS associated with IgG autoantibodies to ECM1. Report of a Case A 64-year-old Japanese woman presented with a 4-year history of pruritic skin lesions on the scalp with hair loss. She denied any significant medical history, the use of particular chemicals, ionizing radiation, or any prior trauma to the region. Clinical examination revealed a 10 × 2.5-cm well-defined ivory plaque with red violaceous papulonodules on the right occipital skin (Figure 1A). No other mucocutaneous eruptions were seen. Differential diagnosis included autoimmune or inflamed sclerotic dermatoses and angiosarcomas. View LargeDownload Figure 1. Clinical and histopathologic images from the subject case. A, The right occipital lesion with scarring alopecia accompanied by red violaceous papulonodules. B, Histologic analysis of a skin biopsy specimen shows hyperkeratosis, epidermal atrophy, edematous dermal papillae, diffuse hyalinization, and homogenized collagen bundles in the dermis (hematoxylin- eosin, original magnification ×25; scale bar indicates 500 μm). C, In addition to pigmentary incontinence, there is capillary dilatation and congestion just beneath the epidermis (hematoxylin-eosin, original magnification ×100; scale bar indicates 100 μm). The results of laboratory investigations, including thyroid function, were normal, and serologic test results for autoimmune diseases and Borrelia burgdorferi were negative. A skin biopsy specimen showed epidermal atrophy with hyperkeratosis, pigmentary incontinence, and hyalinization in the superficial dermis. Skin appendages were replaced by thickened, homogenized collagen bundles, and there were also dilated blood capillaries in the papillary dermis (Figure 1B and C). Elastica van Gieson stain showed a marked decrease in dermal elastic fibers, and the hyalinized dermal component was negatively stained with either alcian blue or colloidal iron. The clinicopathologic findings were consistent with LS. Topical corticosteroid treatment gave symptomatic relief without significant enlargement of the lesion despite the persistent scarring alopecia. Both direct and indirect immunofluorescence findings were negative. Immunoblotting with 3 bacterially expressed ECM1 recombinant fragments that cover the entire ECM1 sequence2 revealed serum IgG reactivity to the distal carboxylic acid (COOH) terminus alone (359-559 amino acids) (Figure 2), which is the region that harbors the immunodominant epitope(s) targeted by serum samples from most patients with anogenital LS.2 The specific IgG reactivity was confirmed by ELISA using the same series of ECM1 recombinants (data not shown).2 View LargeDownload Figure 2. Immunoblotting using a series of bacterially expressed recombinant extracellular matrix protein 1 (ECM1)–glutathione S-transferase fusion fragments. Three distinct recombinant proteins (ΔNH2, ΔS/ex7, and ΔDs/carboxylic acid [COOH]), which cover the entire ECM1 sequence, were immunoblotted independently with the panel of the serum samples, as detailed elsewhere.2 Samples of control genital lichen sclerosus (LS) serum (lane 1), the patient's serum at 1:10 (lane 2) and 1:100 dilutions (lane 3), and anti-ECM1 rabbit serum (lane 5)1 reacted specifically with the ΔDs/COOH recombinant, which is the distal COOH-terminus of ECM1 (amino acids 359-559),2 whereas a healthy volunteer's serum sample (lane 4) did not show any positive reactivity. The patient's serum never reacted with the remaining 2 ECM1 recombinants (data not shown). Arrow indicates the positive signals. Comment Our case report and previous observations2 suggest the common underlying immunopathogenic mechanism associated with humoral autoimmunity to ECM1 in both anogenital and extragenital LS. Therefore, evaluation of ECM1 autoantibody may be a useful approach for serologic diagnosis in LS, regardless of the affected skin sites. An extracellular glycoprotein, ECM1 organizes structural integrity of the dermis and dermoepidermal junction by binding to other structural and extracellular matrix molecules in skin, such as polysaccharides, fibrins, matrix metalloproteinase-9, laminin-332, and collagen IV.3 The autoimmune-based disturbance of ECM1 function may cause the instability of the microskin component assembly, thereby resulting in the establishment of the LS skin disease. Another unique finding includes the clinicopathologic findings similar to those of angiokeratomalike changes in LS.4 Since ECM1 is capable of stimulating vascular endothelial cell proliferation,5 disruption of ECM1 function might also participate in the abnormal configuration of blood vessels. Extragenital LS often represents a diagnostic challenge, particularly with unusual presentation, and serologic screening for the autoimmunity to ECM1 may thus help distinguish LS from other mimicking skin diseases. Back to top Article Information Correspondence: Dr Kawakami, Department of Dermatology, Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima, 960-1295, Japan (kawayoshio@yahoo.co.jp). Financial Disclosure: None reported. Funding/Support: This study was supported by grant NO 21591470 from the Ministry of Education, Science, Sports and Culture of Japan (Dr Oyama). Additional Contributions: Naoko Suzuki and Junko Watanabe provided superb technical assistance. References 1. Oyama NChan INeill SM et al Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet20033629378118123PubMedGoogle Scholar 2. Oyama NChan INeill SM et al Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus. J Clin Invest20041131115501559PubMedGoogle Scholar 3. Sercu SZhang MOyama N et al Interaction of extracellular matrix protein 1 with extracellular matrix components: ECM1 is a basement membrane protein of the skin. J Invest Dermatol2008128613971408PubMedGoogle Scholar 4. Luzar BNeil SMCalonje E Angiokeratoma-like changes in extragenital and genital lichen sclerosus. J Cutan Pathol2009365540542PubMedGoogle Scholar 5. Chan ILiu LHamada TSethuraman G McGrath JA The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol20071611881890PubMedGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

A Case of Lichen Sclerosus of the Scalp Associated With Autoantibodies to Extracellular Matrix Protein 1

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References (5)

Publisher
American Medical Association
Copyright
Copyright © 2009 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archdermatol.2009.313
Publisher site
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Abstract

Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown cause with a predilection for the anogenital area. Recent investigation has identified serum IgG autoantibodies specific to extracellular matrix protein 1 (ECM1) in 74% of patients with anogenital LS1; however, the rationale for humoral autoimmunity to ECM1 in the extragenital disease has been enigmatic. Herein, we describe the first case to our knowledge of extragenital LS associated with IgG autoantibodies to ECM1. Report of a Case A 64-year-old Japanese woman presented with a 4-year history of pruritic skin lesions on the scalp with hair loss. She denied any significant medical history, the use of particular chemicals, ionizing radiation, or any prior trauma to the region. Clinical examination revealed a 10 × 2.5-cm well-defined ivory plaque with red violaceous papulonodules on the right occipital skin (Figure 1A). No other mucocutaneous eruptions were seen. Differential diagnosis included autoimmune or inflamed sclerotic dermatoses and angiosarcomas. View LargeDownload Figure 1. Clinical and histopathologic images from the subject case. A, The right occipital lesion with scarring alopecia accompanied by red violaceous papulonodules. B, Histologic analysis of a skin biopsy specimen shows hyperkeratosis, epidermal atrophy, edematous dermal papillae, diffuse hyalinization, and homogenized collagen bundles in the dermis (hematoxylin- eosin, original magnification ×25; scale bar indicates 500 μm). C, In addition to pigmentary incontinence, there is capillary dilatation and congestion just beneath the epidermis (hematoxylin-eosin, original magnification ×100; scale bar indicates 100 μm). The results of laboratory investigations, including thyroid function, were normal, and serologic test results for autoimmune diseases and Borrelia burgdorferi were negative. A skin biopsy specimen showed epidermal atrophy with hyperkeratosis, pigmentary incontinence, and hyalinization in the superficial dermis. Skin appendages were replaced by thickened, homogenized collagen bundles, and there were also dilated blood capillaries in the papillary dermis (Figure 1B and C). Elastica van Gieson stain showed a marked decrease in dermal elastic fibers, and the hyalinized dermal component was negatively stained with either alcian blue or colloidal iron. The clinicopathologic findings were consistent with LS. Topical corticosteroid treatment gave symptomatic relief without significant enlargement of the lesion despite the persistent scarring alopecia. Both direct and indirect immunofluorescence findings were negative. Immunoblotting with 3 bacterially expressed ECM1 recombinant fragments that cover the entire ECM1 sequence2 revealed serum IgG reactivity to the distal carboxylic acid (COOH) terminus alone (359-559 amino acids) (Figure 2), which is the region that harbors the immunodominant epitope(s) targeted by serum samples from most patients with anogenital LS.2 The specific IgG reactivity was confirmed by ELISA using the same series of ECM1 recombinants (data not shown).2 View LargeDownload Figure 2. Immunoblotting using a series of bacterially expressed recombinant extracellular matrix protein 1 (ECM1)–glutathione S-transferase fusion fragments. Three distinct recombinant proteins (ΔNH2, ΔS/ex7, and ΔDs/carboxylic acid [COOH]), which cover the entire ECM1 sequence, were immunoblotted independently with the panel of the serum samples, as detailed elsewhere.2 Samples of control genital lichen sclerosus (LS) serum (lane 1), the patient's serum at 1:10 (lane 2) and 1:100 dilutions (lane 3), and anti-ECM1 rabbit serum (lane 5)1 reacted specifically with the ΔDs/COOH recombinant, which is the distal COOH-terminus of ECM1 (amino acids 359-559),2 whereas a healthy volunteer's serum sample (lane 4) did not show any positive reactivity. The patient's serum never reacted with the remaining 2 ECM1 recombinants (data not shown). Arrow indicates the positive signals. Comment Our case report and previous observations2 suggest the common underlying immunopathogenic mechanism associated with humoral autoimmunity to ECM1 in both anogenital and extragenital LS. Therefore, evaluation of ECM1 autoantibody may be a useful approach for serologic diagnosis in LS, regardless of the affected skin sites. An extracellular glycoprotein, ECM1 organizes structural integrity of the dermis and dermoepidermal junction by binding to other structural and extracellular matrix molecules in skin, such as polysaccharides, fibrins, matrix metalloproteinase-9, laminin-332, and collagen IV.3 The autoimmune-based disturbance of ECM1 function may cause the instability of the microskin component assembly, thereby resulting in the establishment of the LS skin disease. Another unique finding includes the clinicopathologic findings similar to those of angiokeratomalike changes in LS.4 Since ECM1 is capable of stimulating vascular endothelial cell proliferation,5 disruption of ECM1 function might also participate in the abnormal configuration of blood vessels. Extragenital LS often represents a diagnostic challenge, particularly with unusual presentation, and serologic screening for the autoimmunity to ECM1 may thus help distinguish LS from other mimicking skin diseases. Back to top Article Information Correspondence: Dr Kawakami, Department of Dermatology, Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima, 960-1295, Japan (kawayoshio@yahoo.co.jp). Financial Disclosure: None reported. Funding/Support: This study was supported by grant NO 21591470 from the Ministry of Education, Science, Sports and Culture of Japan (Dr Oyama). Additional Contributions: Naoko Suzuki and Junko Watanabe provided superb technical assistance. References 1. Oyama NChan INeill SM et al Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet20033629378118123PubMedGoogle Scholar 2. Oyama NChan INeill SM et al Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus. J Clin Invest20041131115501559PubMedGoogle Scholar 3. Sercu SZhang MOyama N et al Interaction of extracellular matrix protein 1 with extracellular matrix components: ECM1 is a basement membrane protein of the skin. J Invest Dermatol2008128613971408PubMedGoogle Scholar 4. Luzar BNeil SMCalonje E Angiokeratoma-like changes in extragenital and genital lichen sclerosus. J Cutan Pathol2009365540542PubMedGoogle Scholar 5. Chan ILiu LHamada TSethuraman G McGrath JA The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol20071611881890PubMedGoogle Scholar

Journal

Archives of DermatologyAmerican Medical Association

Published: Dec 1, 2009

Keywords: extracellular matrix proteins,autoantibodies,lichen sclerosus atrophicus,scalp

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