CASE REPORT Clinical and Experimental Rheumatology 2000; 18: 622-624.

Physical injury as a ABSTRACT cirrhosis were found on ultrasound ex- A 51-year-old female developed linear- amination. provoking factor in like scleroderma in the left thigh In 1975, plaques characteristic of lichen three patients with following a linear wound caused by a ruber planus appeared on both buttocks car accident. 27 years later she also following several intramuscular injec- scleroderma developed a typical diffuse cutaneous tions. In 1983, symmetric polyarthralgia systemic sclerosis with extensive skin in the metacarpophalangeal and proxi- A. Komócsi, E. Tóvári, involvement and bibasilar pulmonary mal interphalangeal joint lines were de- 1 fibrosis. The second case is a 39-year- tected without any classical signs of in- J. Kovács , L. Czirják old female who had a history of flammation. A positive LE test, a homo- Raynaud’s phenomenon since early geneous antinuclear antibody staining Nephrological Center and 2nd Department childhood. She developed a morphea pattern (on rat liver section), and a mod- of Internal Medicine, University Medical following a burning injury of the left erately elevated Waaler-Rose titer were 1 School of Pécs, Pécs; Department of thigh. 17 years later she also devel- also found. In 1985, a bronchopneumo- Pathology, University Medical School of oped a typical limited cutaneous nia with a septic-toxic state was detected Debrecen, Debrecen; Hungary. systemic sclerosis with sclerodactyly, and cured. In the following years, apart András Komócsi, MD; Eszter Tóvári, MD; skin ulcers and subcutaneous calcino- from polyarthralgia, the patient was heal- Judit Kovács, MD, PhD; László Czirják MD, D.Sc. sis. The third case is a 43-year-old thy and asymptomatic. The local skin female who developed a typical involvement of the thigh remained sta- Please address correspondence and reprint morphea of the right elbow around the ble. Regarding the laboratory findings, requests to: Dr. László Czirják, University of Pécs, Medical Faculty, Nephrological site of a previous local corticosteroid a permanently elevated ESR (between Center and 2nd Department of Internal injection. The two remarkable points of 50-80 mm/hr) and a polyclonal increase Medicine, Clinical Immunology Unit, these 3 cases are the possible role of in the IgG level were detected. Pacsirta u. 1, H-7624 Pécs, Hungary. physical injury in the provocation of In 1990, skin symptoms characteristic of E-mail: [email protected] localized scleroderma and in the first 2 rapidly progressive diffuse cutaneous © Copyright CLINICAL AND cases the unusual later development of systemic sclerosis were detected, involv- EXPERIMENTAL RHEUMATOLOGY 2000. a systemic form of scleroderma. ing the trunk, face, and the extremities. The skin involvement which was histolo- Key words: Localized scleroderma, Introduction gically confirmed by a skin biopsy from systemic sclerosis, physical injury. Certain physical effects, including limb the forearm, was accompanied by exten- immobilization (1), spinal cord injury (2) sive hypo-hyperpigmentation and a bi- and radiation therapy (3, 4), may pro- basilar lung fibrosis with restrictive ven- voke scleroderma. Other forms of physi- tilatory failure. No other internal organ cal injury, including local injection, have involvement, myositis, or Raynaud’s also been described as possible provok- phenomenon were detected. No anti- ing factors of localized scleroderma (5- Borrelia, anti-Rnp, anti-topoisomerase I, 8). In the present study 3 patients are anti-centromere, and anti-nucleolar an- described who developed localized scle- tibodies were found. A homogeneous roderma following mechanical injury staining patter of antinuclear antibody (wound formation following a traffic (on HEp-2 cells) was found without the accident, thermal injury, and the effect presence of anti-dsDNA antibody. of a local injection). In 1990, a combination of D-penicilla- mine (300-450 mg/day), pentoxyfyllin Case histories (800 mg/day), and nifedipine (30 mg/ Case 1 day) therapy was introduced. The pro- A 51-year-old female patient suffered a gression of the skin symptoms stopped 20 cm longitudinal elongated wound, on 10 months later. The patient’s condition the left thigh during a traffic accident in became stable without any fluctuation in 1973. Six months following this local the following years. No signs of serious physical injury, a linear, scleroderma-like liver disease have been observed. lesion developed on the site of the former lesion. The histological investigation Case 2 proved the typical signs of scleroderma A 39-year-old female had a history of (Fig. 1). No other sites of the skin were Raynaud’s phenomenon involving sym- involved. The patient was a chronic al- metrically both hands since her early coholic with a possible intake of between childhood. In 1980, at the age of 21, she 10-50 g/day. No signs of liver or biliary spilt boiling water on the extensor sur-

622 Scleroderma and physical injury / A. Komócsi et al. CASE REPORT

(a) (b) Fig. 1. (a) A linear scleroderma-like lesion at the site of a former elongated wound (Case 1). (b) Histological investigation demonstrated the typical signs of scleroderma with lymphocytic infiltrate around the eccrine glands (Case 1) (hematoxyllin and eosin staining, 160x). face of her left thigh. Months later a le- sclerodactyly. X-ray studies revealed a garding the investigation of the internal sion of typical morphea appeared in the subcutaneous calcinosis on the second organs, mild bibasilar lung fibrosis was affected area. Although the skin involve- phalanx of the left second finger and found on the chest x-ray and was con- ment was not confirmed by biopsy, the signs of mild bibasilar lung fibrosis. The firmed by high resolution computed to- lesion was described as morphea several latter was confirmed by high resolution mography. The latter did not show any times. In the following years the lesion computer tomography. No anticentro- signs suggesting the presence of alveo- became atrophic and some hypopigmen- mere antibody was detected. The find- litis. Spirometry values were normal ex- tation appeared and this condition re- ings described above were compatible cept a slightly diminished CO diffusion mained stable. In 1982, while the previ- with the development of limited cutane- coefficient. The antinuclear antibody test ous sites of morphea became more pro- ous systemic sclerosis. on HEp-2 cells was negative. nounced, the lower left quadrant of the abdominal skin became slightly hyper- Case 3 Discussion pigmented and indurated lesions appear- A 43-year-old female received a peri- Several provoking factors may contrib- ed. The abdominal skin was not previ- articular corticosteroid injection to the ute to the development of scleroderma. ously affected by the thermal injury. In lateral part of the right elbow in 1999, a We have previously described that ex- 1983 several tests were performed, in- few months before her first visit to our posure to certain chemicals including cluding: chest x-ray, barium swallow, department. The indication for the ad- organic solvents, are important provok- hand and feet x-rays, Schirmer’s test and ministration of this therapy remained ing agents of scleroderma among Hun- nailfold capillary microscopy. At that obscure; probably the presence of peri- garian cases (9). Regarding physical in- time none of the investigations or labo- ostitis was presumed. A few weeks later jury, limb immobilization (1), spinal cord ratory data showed any signs of systemic typical morphea (confirmed by biopsy) injury (2), and radiation therapy (3, 4), scleroderma. In 1986 a skin ulcer ap- was noticed around the site of the injec- have been reported as possible provok- peared over the left lateral ankle. Since tion (Fig. 2). No other sites of the body ing factors for scleroderma. All 3 patients that time repeated skin ulcers have ap- were affected. We did not detect joint described above also developed a local- peared in that area. Both the arterial and symptoms, and an x-ray of the right el- ized form of scleroderma (linear-like the venous circulation of this extremity bow did not show any abnormality. Re- scleroderma and morphea) following a were found to be normal. Since 1990 antinuclear antibody positi- vity was reported on rat liver sections. The antibody showed homogeneous nu- clear staining on HEp-2 cell cultures without anti-dsDNA positivity. Nailfold capillary microscopy described isolated apical widening of the capillary loops, but no abnormalities diagnostic of scle- roderma were detected. In 1997, the patient was admitted with complaints of Raynaud‘s phenomenon, slightly decreased maximal oral aperture, Fig. 2. Signs of morphea and facial teleangiectasia. The skin of the following a local cortico- fingers was tight, but not to the extent of steroid injection (case 3).

623 CASE REPORT Scleroderma and physical injury / A. Komócsi et al. local physical injury. scleroderma, but this seems to be a rather GARCIA A: Post-traumatic nodular scleroder- Our first case is unusual for diffuse scle- exceptional finding. ma. Med Cutan Ibero Lat Am 1983;11:329-32. roderma because, in spite of the exten- The vascular endothelial injury which is 7. ALONSO-LLAMAZARES J, AHMED I: Vitamin K1-induced localized scleroderma (morphea) sive skin involvement, a relative lack of a hallmark of scleroderma, may be me- with linear deposition of IgA in the basement internal organ manifestations was ob- diated by several mechanisms including membrane zone. J Am Acad Dermatol 1998; served. Such a physical injury as a pos- decreased endothelial expression of the 38: 322-4. sible provoking factor of scleroderma complement protective molecular sys- 8. BELLMAN B, BERMAN B: Localized indurated brown plaques on arms and right buttock. Pen- skin lesions has not been previously de- tem, white blood cell activation through tazocine-induced morphea. Arch Dermatol scribed. the production of free radicals, and fur- 1996; 132: 1366-7,1368-9. In the second patient the appearance of thermore an altered production of neuro- 9. CZIRJÁK L, DANKÓ K, SCHLAMMADINGER J, morphea was followed by the burns as peptides (19-21). The exact neuronal- SURÁNYI P, TAMÁSI L, SZEGEDI GY: Progres- sive systemic sclerosis occurring in patients physical injury and later a limited cutane- related mechanisms are not well charac- exposed to chemicals. Int J Dermatol 1987; ous systemic sclerosis developed. These terised, but the development of sclero- 26: 374-8. 2 patients exhibit a certain similarity to derma-like dermal changes following 10. RAHMAN MA, JAYSON MI, BLACK CM: Five the cases reported by Rahman et al., who spinal cord injury suggests an important patients who developed systemic sclerosis shortly after episodes of physical trauma. J described 5 cases who developed sys- role for neuronal participation in the de- Rheumatol 1996; 23: 1816-7. temic sclerosis shortly after episodes of velopment of scleroderma. 11. SOMA Y, TAMAKI T, KIKUCHI K et al.: Coex- trauma. But in these cases, the site of Manual vibration exposure as a special istence of morphea and systemic sclerosis. injury showed no signs of localised scle- form of mechanical injury can also in- Dermatology 1993; 186: 103-5. 12. ROSSI P, FOSSALUZZA V, GONANO L: Local- roderma (10). The difference is that in duce Raynaud’s phenomenon and, occa- ized scleroderma evolving into systemic scle- our 2 patients, besides the systemic scle- sionally, sclerodactyly (16-18). Vibra- rosis. J Rheumatol 1985; 12: 629-30. roderma, the local trauma also caused tion-induced direct damage of blood ves- 13. MIZUTANI H, TANAKA H, OKADA H, MIZU- localised scleroderma. sels causes a disturbed local microcir- TANI T, SHIMIZU M: Palindromic morphea: Multiple recurrence of morphea lesions in a Regarding the third patient, an injection culation. Recent studies also indicate that case of systemic sclerosis. J Dermatol 1992; as a physical injury provoked the appear- the neuronal deficit formerly identified 19: 298-301. ance of morphea, a phenomenon which by immunohistochemistry in the digital 14. BIRDI N, LAXER RM, THORNER P, FRITZLER has been previously described in only a skin of patients with vibration white fin- MJ, SILVERMAN ED: Localized scleroderma progressing to systemic disease. Case report few patients (5-8). Antitetanical vacci- ger (22) has a functional counterpart in and review of the literature. Arthritis Rheum nation, vitamin K1 and pentazocin were vivo and is evident as a reduced ability 1993; 36: 410-5. described as causing morphea following to propagate an axon-reflex vasodilator 15. CZIRJÁK L, LADÁNYI É, SCHLAMMADINGER local injection (6-8). Similar to our case, response when challenged with hista- J, SZEGEDI G: Signs of systemic disease in lo- calized scleroderma. Arch Dermatol Res 1991; a sclerodermiform linear atrophy follow- mine and endothelin-1 (23). 283: 418. ing the administration of intralesional In our cases, mechanical injury may have 16. NAGATA C, YOSHIDA H, MIRBOD SM et al.: corticosteroids for periorbital hemangio- caused vascular endothelial damage and Cutaneous signs (Raynaud’s phenomenon, mas has recently also been described (5). neuronal injury which could be impor- sclerodactylia, and edema of the hands) and hand-arm vibration exposure. Int Arch Occup In our case, the administration of local tant contributing factors to the develop- Environ Health 1993; 64: 587-91. steroid may have also played a role in ment of trauma induced scleroderma. 17. MAEDA M, ICHIKI Y, SHIKANO Y, MORI S, the provocation of morphea. KITAJIMA Y: Detection of scleroderma with ca- Although it has been recently demon- References pillaroscopic abnormalities of nailfolds. Int J Dermatol 1996; 35: 857-61. strated that the coexistence of SSc and 1. VARGA J, JIMENEZ SA: Development of severe limited scleroderma in complicated Raynaud’s 18. BLAIR HM, HEADINGTON JT, LYNCH PJ: Oc- morphea may not be an entirely unusual phenomenon after limb immobilization: report cupational trauma, Raynaud phenomenon, and event (11-13), patients with localized of two cases and study of collagen biosynthe- sclerodactylia. Arch Environ Health 1974; 28: scleroderma rarely develop symptoms sis. Arthritis Rheum 1986; 29: 1160-5. 80-1. characteristic of systemic sclerosis (SSc) 2. STOVER SL, GAY RE, KOOPMAN W, SAHGAL 19. MATUCCI CERINIC M: Sensory neuropeptides V, GALE LL: Dermal fibrosis in spinal cord in- and rheumatic diseases. Rheum Dis Clin North

(14). Both autoantibodies as well as in- jury patients: a scleroderma variant ? Arthritis Am 1993; 19: 975-91. ternal organs symptoms and microvas- Rheum 1980; 23: 1312-7. 20. KAHALEH MB: Raynaud’s phenomenon and cular injury can be observed in localized 3. DAVIS DA, COHEN PR, MCNEESE MD, DUVIC the vascular disease in scleroderma. Curr Opin scleroderma, which is a well defined and M: Localized scleroderma in breast cancer pa- Rheumatol 1995; 7: 529-34. tients treated with supervoltage external beam 21. CZIRJÁK L, DANKÓ K, SIPKA S, ZEHER M, strictly different disease entity from the radiation: radiation port scleroderma. J Am SZEGEDI G: Polymorphonuclear neutrophil diffuse form of SSc. In our 2 patients the Acad Dermatol 1996; 35: 923-7. function in systemic sclerosis. Ann Rheum Dis localized SSc became combined with the 4. GOLLOB MH, DEKOVEN JG, BELL MJ, ASSA- 1987; 46: 302-6. systemic form of the disease. Further- AD D, RAO J: Postradiation morphea. J Rheu- 22. GOLDSMITH PC, MOLINA FA, BUNKER CB et matol 1998; 25: 2267-9. al.: Cutaneous nerve fibre depletion in vibra- more, the third case also seems to have 5. VAZQUEZ BOTET R, REYES BA, VAZQUEZ tion white finger. J R Soc Med 1994; 87: 377- some systemic involvement, i.e. lung fi- BOTET M: Sclerodermiform linear atrophy af- 81. brosis. As we have previously described ter the use of intralesional steroids for perior- 23. DOWD PM, GOLDSMITH PC, CHOPRA S, BULL (15), internal organ manifestations in- bital hemangiomas: A review of complications. HA, FOREMAN JC: Cutaneous responses to J Pediatr Ophthalmol Strabismus 1989; 26: endothelin-1 and histamine in patients with vi- cluding pulmonary fibrosis may occa- 124-7. bration white finger. J Invest Dermatol 1998; sionally occur in patients with localized 6. BONINO MV, BIANCHI C, BIANCHI O, GARCIA 110: 127-31.

624