Isomorphic and symmetric adult-onset generalized morphea are associated with distinctive clinical features: A retrospective multicenter study
Authors: Antoine Braud, Antoine Mahé, Catherine Michel, Bernard Cribier, Dan Lipsker, Cédric Lenormand
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: Generalized morphea (GM) is a rare subtype of localized scleroderma characterized by widespread involvement. GM is defined by the presence of at least 4 lesions larger than 3 cm that involve at least 2 anatomic sites.1Laxer R.M. Zulian F. Localized scleroderma.Curr Opin Rheumatol. 2006; 18: 606-613Crossref PubMed Scopus (243) Google Scholar Isomorphic and symmetric subsets of GM were recently delineated based on a computerized lesion mapping approach.2Teske N. Welser J. Jacobe H. Skin mapping for the classification of generalized morphea.J Am Acad Dermatol. 2018; 78: 351-357Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar In the isomorphic pattern, the lesions favor areas of skin friction (ie, brassiere band, waistband, inguinal creases), whereas in the symmetric one, they occur with a symmetric distribution on the trunk and extremities. A higher frequency of deep involvement was reported in patients with symmetric GM, whereas lichen sclerosus-like changes were a frequent finding in morphea plaques from patients with isomorphic GM.2Teske N. Welser J. Jacobe H. Skin mapping for the classification of generalized morphea.J Am Acad Dermatol. 2018; 78: 351-357Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar This retrospective study aimed to describe the clinical characteristics of another cohort of patients with adult-onset GM and to investigate if further differences exist between isomorphic and symmetric subsets. We conducted a retrospective chart review of 27 patients followed up for GM in 3 hospitals from the east of France between 2009 and 2019. Cases were identified using the international coding for morphea (L94.0 in the International Classification of Diseases, 10th revision). Data including demographics, comorbidities, and laboratory findings were retrieved. Two investigators (AB and CL) independently reviewed the photographs to categorize patients into isomorphic or symmetric subsets, when possible, using the skin mapping recently published.2Teske N. Welser J. Jacobe H. Skin mapping for the classification of generalized morphea.J Am Acad Dermatol. 2018; 78: 351-357Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar A third blinded investigator (DL) was involved in case of disagreement. Comparison between subsets was made using the Student t test and Fisher's exact test. Interrater agreement was assessed with the Cohen kappa test. The relevant demographic characteristics and patient comorbidities are summarized in Table I. All patients had undergone systematic genital examination. Fifteen patients (56%) had genital lichen sclerosus, and 9 (33%) had autoimmune comorbidities. Twenty-three patients (85%) could be classified into either the isomorphic (n = 12) or symmetric (n = 11) subsets. The 4 remaining unclassed patients had either features of both subsets or none. Cohen's kappa was 0.88, suggesting a very good agreement between raters in favor of the applicability of this classification.Table IDemographic characteristics and associated comorbidities of GMCharacteristicsValuePatients, N27Sex Female, n (%)21 (78) Male, n (%)6 (22) F:M3.5:1Age of onset, y, mean (SD)60 (11)Time to diagnosis, mo, mean (SD)18 (26)Genital lichen sclerosus, n (%)15 (56)Autoimmune comorbidities, n (%)9 (33) Autoimmune thyroiditis2 Inflammatory bowel disease1 Alopecia areata1 Systemic lupus erythematosus1 Spondyloarthropathy1 Psoriasis1 Rheumatoid arthritis1 Polymyalgia rheumatica1F, Female; M, male; SD, standard deviation. Open table in a new tab F, Female; M, male; SD, standard deviation. The comparative clinical and biological characteristics are summarized in Table II. Sex and age at onset were equivalent between the 2 groups. Genital lichen sclerosus was strikingly more frequent in patients with the isomorphic subset (10/12 vs 4/11; P = .04), whereas patients with symmetric GM more often had autoimmune comorbidities (1/12 vs 6/11; P = .03).Table IIComparison between isomorphic and symmetric GMCharacteristicsIsomorphic GMSymmetric GMP∗P < .05 was considered significant.Patients, n (%)†Four patients did not fit into either subset.12 (52)11 (48)Sex, n (%) Female10 (83)8 (73).64 Male2 (17)3 (27)Age at onset, y, mean (SD)63 (12)57 (10).20Pruritus, n (%)4 (33)7 (64).22Functional impairment, n (%)0 (0)3 (27).09Genital lichen sclerosus, n (%)10 (83)4 (36).04Autoimmune comorbidities, n (%)1 (8)6 (54.5).03Antinuclear antibodies positivity, n/total (%)‡≥1/160; only 17 patients were tested (7 isomorphic, 11 symmetric).1/7 (14)4/10 (40).34GM, Generalized morphea; SD, standard deviation. Bold text signifies statistical significance (<.05).∗ P < .05 was considered significant.† Four patients did not fit into either subset.‡ ≥1/160; only 17 patients were tested (7 isomorphic, 11 symmetric). Open table in a new tab GM, Generalized morphea; SD, standard deviation. Bold text signifies statistical significance (<.05). We found an even higher prevalence of genital lichen sclerosus than already reported in patients with classical morphea.3Lutz V. Francès C. Bessis D. et al.High frequency of genital lichen sclerosus in a prospective series of 76 patients with morphea: toward a better understanding of the spectrum of morphea.Arch Dermatol. 2012; 148: 24-28Crossref PubMed Scopus (32) Google Scholar This prevalence peaked in the subgroup of patients with isomorphic GM, whereas patients with symmetric GM had a higher frequency of autoimmune comorbidities. Despite its retrospective design and small sample, our study strongly supports the clinical relevance of this dichotomous classification. Taken together, the findings published by Teske et al2Teske N. Welser J. Jacobe H. Skin mapping for the classification of generalized morphea.J Am Acad Dermatol. 2018; 78: 351-357Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar and our results suggest that lichen sclerosus, whether in a genital location or not, may represent the most superficial manifestation in the spectrum of morphea, where subtle repetitive trauma would play a determinant pathophysiologic role.