Letters to the Editors

Evolution of one systemic rheumatic disease into another: evolving to eosinophilic with

Sirs, A 33-year-old woman developed systemic sclerosis (SSc) six years ago manifesting initially with puffy hands, Raynaud’s phe- nomenon, fingertip ulcers and small hand joints arthritis. Subsequently, progressive skin thickening of fingers/hands (sclero- dactyly), face, limbs and abdomen ensued along with facial and chest wall telangiec- tasias and oral aperture reduction. Further- more, the last three years incipient pulmo- nary fibrosis was diagnosed. From diagno- sis anti-nuclear antibodies (ANA, 1:1280, nucleolar pattern) and rheumatoid factor (RF, 150IU/ml, normal range (n.r.) <15IU/ ml) were present while anti-Scl70 antibody was negative. She was treated with metho- trexate s.c. (20mg/week) and occasionally low dose oral methylprednisolone. Silde- nafil 20mg t.i.d. was given during- win Fig. 1. Full-thickness wedge biopsy, including skin, subcutis, and muscle, of the inner side of the right arm. ter months to combat digital ulcers. Six (A) The epidermis is thin and atrophic. The middle and lower show a marked thickening of dermal collagen months ago, during her last scheduled eval- with overall paucity of adnexal structures, loss of periadnexal fat as well as thickening and luminal narrowing of uation, the patient complained of myalgias, small vessel blood vessels (H&E, X40). (B) In the deeper layers, fascial thickening and , perivascular without preceding intense physical activity. inflammation along with accumulation of lymphocytes and macrophages is seen, findings suggestive of eosinophilic Clinical examination revealed an intense fasciitis (Masson’s Trichrome, X40). (C, D) In the muscle layer, inflammation with muscle fibres invaded by lympho- peau d’orange appearance of skin of both cytes (arrowhead), vacuolar muscle fibres (arrows), necrotic fibres with phagocytosis (asterisks), and perifascicular atrophy are evident, findings suggestive of myositis (H&E, X200). brachial areas, thighs and abdomen. Muscle strength was normal, while sclerodactyly of hands and feet had remarkably regressed. (0.5mg/kg body-weight/day) and azathio- timately the same, namely fibrosis, patients Laboratory tests showed peripheral eosino- prine (2.5mg/kg body-weight/day) were present with different clinical features. To philia (820/μL), diffuse hypergammaglob- initiated. One month later, clinical and lab- date it is not known whether these diseases ulinaemia (γ-globulins 20%) and elevated oratory improvement was noticeable. share a common pathogenic pathway. There serum CPK 1397U/L (n.r.<192U/L), AST We present this case firstly because evolu- are however few gene expression microar- 115U/L (n.r.<35), ALT 86U/L (n.r.<43) and tion or overlap of SSc with EF and sub- ray studies performed on skin or fibroblasts LDH 704U/L (n.r.<214U/L). Acute phase jacent myositis has been described ex- from patients with SSc and EF suggesting reactants (C-reactive-protein, erythrocyte- ceedingly rarely in the literature (1), and that gene expression of the skin biopsy sedimentation-rate) and thyroid hormones to point out how a systemic autoimmune from EF patients is clustered close to dif- were within normal range, while the pres- disease may evolve into another through fuse proliferative SSc (6), which could be ence of anti-Pm/Scl75 and anti-Pm/Scl100 sequential involvement of different organs/ a possible explanation of the observed se- positivity was found for the first time. systems (2). Systemic autoimmune rheu- quential autoimmune reaction towards sim- With the suspected diagnosis of eosinophil- matic diseases can present with at times ilar molecular targets. ic fasciitis (EF) with muscle involvement, erratic clinical phenotype. In some patients a full-thickness wedge biopsy, including the disorder can run a mild, subclinical E. Zampeli1, MD, PhD skin, subcutis, fascia and muscle, from the course, while in others it can be a severe, A. Pantelidaki2, MD 1,3,4 inner side of one arm was obtained. life-threatening disorder. Furthermore, H.M. Moutsopoulos , MD, FACP The biopsy showed typical skin histo- some patients can initially present with the FRCP(hc), Master ACR 1 logical findings of scleroderma, including clinical phenotype of one disorder, as our Institute for Autoimmune Systemic and marked thickening of dermal collagen, loss patient, and after a disease course of some Neurological Diseases, Athens; 2Pathologist, Michalakopoulou 42, Athens; of periadnexal fat, compression of adnexal years they may manifest characteristics of 3Academy of Athens; structures as well as thickening and luminal other rheumatic disorders. 4Department of Pathophysiology, Medical narrowing of small vessel (Fig. 1A). In the EF is an uncommon scleroderma-mimick- School, National and Kapodistrian University deeper layers, perivascular inflammation ing disease entity characterised by symmet- of Athens, Greece. along with fascial thickening and accumu- ric swelling of the extremities and the trunk Please address correspondence to: lation of lymphocytes and macrophages progressing to sclerosis of the mid and deep Dr Evangelia Zampeli, was seen (Fig. 1B); findings compatible dermis, subcutaneous fat and fascia. Institute for Systemic Autoimmune with EF. In the muscular layer inflamma- Internal organ involvement is exception- and Neurological Diseases, ally rare and induration typically spares the M. Asias 75, 11527, Athens, Greece. tion with lymphocytic infiltration, phagocy- E-mail: [email protected] tosis, necrotic fibres and perifascicular atro- digits, features distinguishing EF from SSc phy (Fig. 1C-D), was evident, histological (3-5). SSc and EF are both inflammatory Competing interests: none declared. findings suggestive of myositis. Methotrex- skin fibrotic disorders. Although the pheno- © Copyright Clinical and ate was discontinued and oral prednisolone typic end-stage of these two diseases is ul- Experimental 2019.

Clinical and Experimental Rheumatology 2019 S-149 Letters to the Editors

References 2018; 87: e12657. 5. FETT N, ARTHUR M: Eosinophilic fasciitis: 1. DROSOS AA, PAPADIMITRIOU CS MOUTSOPOU- 3. MOUTSOPOULOS HM, WEBBER BL, PAVLIDIS Current concepts. Clin Dermatol 2018; 36: 487-97. LOS HM: An overlap of diffuse fasciitis with eo- NA, FOSTIROPOULOS G, GOULES D SHULMAN 6. LIMPERS A, van ROYEN-KERKHOF A, van ROON sinophilia and scleroderma. Rheumatol Int 1984; 4: LE: Diffuse fasciitis with . A clinico- JA, RADSTAKE TR, BROEN JC: Overlapping gene 187-89. pathologic study. Am J Med 1980; 68: 701-9. expression profiles indicative of antigen processing 2. KARAGIANNI P, ZAMPELI E, MOUTSOPOULOS 4. PINAL-FERNANDEZ I, SELVA-O’ CALLAGHAN A and the interferon pathway characterize inflamma- HM: Evolution from one autoimmune disorder GRAU JM: Diagnosis and classification of eosino- tory fibrotic skin diseases.Expert Rev Clin Immunol to another. Epitope spreading? Scand J Immunol philic fasciitis. Autoimmun Rev 2014; 13: 379-82. 2014; 10: 231-41.

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