Beneficial effect of immunosuppressive drugs on Parry-Romberg syndrome: a case report and review of the literature.

Abstract: Progressive facial hemiatrophy, also known as Parry-Romberg syndrome (PRS), is characterized by slowly progressive atrophy of one side of the face, primarily involving the subcutaneous tissues and fat. Involvement of the central nervous system with impairment of neurologic function occurs infrequently. At present, there is no agreement as to whether PRS is a distinct entity or a clinical variant of linear scleroderma en coup de sabre. The exact reason for PRS has not yet been determined; therefore, no suitable treatment exists. We observed beneficial effects of immunosuppressive agents on neurologic lesions in particular in a patient with PRS who presented with immunoinflammatory findings and neurologic involvement, apart from cutaneous manifestations.

Key Words: progressive facial hemiatrophy, Parry-Romberg syndrome, linear scleroderma en coup de sabre, inflammation, immunosuppressive treatment

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Progressive facial hemiatrophy, also known as Parry-Romberg syndrome (PRS), is characterized by slowly progressive atrophy of one side of the face, primarily involving the subcutaneous tissues and fat. (1) Involvement of the central nervous system with impairment of neurologic function occurs infrequently. There have been occasional reports of epileptic seizures, vascular headaches, hemiparesis, or ophthalmologic abnormalities in this syndrome. (2) At present, there is no agreement as to whether PRS is a distinct entity or a clinical variant of linear scleroderma en coup de sabre (LSCS). Whereas some authors prefer to distinguish PRS from LSCS, (2,3) others do not recognize the former as a separate clinical entity. (3) Most authors agree that PRS and LSCS have overlapping clinical and laboratory findings. (4) The exact reason for PRS has not been determined; therefore, no suitable treatment exists as yet. We present a PRS case with immunoinflammatory findings and discuss the inflammatory nature of PRS and its good response to immuno-suppressive drugs. This case report supports previous results suggesting that immunosuppressive drugs could be effective in improving some symptoms of PRS. (5,6)

Case Report

In July 2001, a 20-year-old, right-handed man presented with 2 years' history of alopecia in the left frontoparietal region. The patient had been aware of a progressive atrophy of the left side of his face since 2000. He had also noted shrinkage of the left side of his tongue and hemimasticatory spasm.

Physical examination revealed left-sided hemiatrophy of the face and atrophy of the left side of the tongue. He had alopecia of his left frontoparietal region, with eyebrow and upper eyelash shedding on the right side of the left eye. The moustache and beard on the left side of his face had also shed (Fig. 1). Laboratory investigations revealed an erythrocyte sedimentation rate of 12 mm/h; C-reactive protein, 1.4 mg/dL (n < 0.8 mg/dL); IgM rheumatoid factor, 85.1 IU/mL (n < 15 IU/mL); IgG, 1950 mg/dL (n = 751 to 1560); and IgM, 345 (n = 46 to 304). The other laboratory tests were within normal limits. The biopsy specimen taken from the left chin showed minimal homogenization of the dermal collagen fibers and moderate perivascular mononuclear cells infiltration in the dermal vessels.

Methotrexate (MTX) and methylprednisolone were commenced in the doses of 7.5 mg/wk and 32 mg/d, respectively. The latter drug was discontinued gradually within 8 weeks. In August 2002, a generalized tonic-clonic seizure developed 3 weeks after MTX had been discontinued in preparation for an esthetic operation.

Coronal [T.sub.2]-weighted cerebral MRI showed a hyper-intense lesion located on the posterior genu of capsula interna extending through lentiform nucleus to thalamus (Fig. 2A). Cerebral MRI angiography showed an increase in the calibration of the left internal carotid artery as well as vascular crowding around the retro-orbital region and a conspicuous ophthalmic artery. Due to family reluctance, the operation was canceled, and the MTX dosage was increased to 15 mg/per week plus folic acid and carbamazepine. The lesion decreased in size when viewed after 2 years (Fig. 2B), but vascular abnormalities did not change. Although rheumatoid factor titers declined to nearly normal levels (25 IU/mL), increased levels of immunoglobulin and C-reactive protein returned to normal levels during the follow-up period. Clinically, the patient's hemimasticatory spasms completely disappeared, and a beard that required shaving grew on the left side of his face. However, no change was observed in his left-sided hemiatrophy and alopecia. Carbamazepine was discontinued after 18 months due to seizure cessation, and the patient remains on small doses of MTX. No recurrence of seizures has been observed thus far.

Discussion

The pathogenesis of PRS is uncertain as yet. No agreement has been achieved on whether PRS is a distinct entity or a clinical variant of LSCS, characterized by a band-like distribution of dermal induration extending above the level of the eyelid from the forehead to the central scalp. Although some authors prefer to distinguish PRS from LSCS, (2,3) others do not recognize the former as a separate clinical entity. (4) Most authors agree that PRS and LSCS have overlapping clinical and laboratory findings. (7)

Anti-nuclear antibody, anti-DNA, and rheumatoid factor positivity as well as increased IgG levels also have been reported in PRS. (4,8) In PRS, skin biopsy specimens reveal chronic inflammation with atrophy of hair follicles and subcutaneous fat. (9,10) Uveitis, retinal vasculitis, and cutaneous vasculitis have all been reported in PRS. (11,12) Fernandez et al (13) described PRS as a form of focal vasculitis. Felipe et al (14) conducted a neuropathological study in a patient with PRS, in which neuronal loss, gliosis, and activated microglial cells strongly immunolabeled by HLA-DR were found in dentate gyrus.

[FIGURE 1 OMITTED]

Studies reporting an association between PRS and some autoimmune diseases, such as systemic lupus erythematosus (15) and scleroderma, (16) support the concept that PRS has autoimmune diathesis. It can be concluded from these reports that PRS may have an immunoinflammatory nature similar to that of LSCS, which has even prompted some authors to use immunosuppressive drugs in the treatment of PRS, especially in the cerebral involvement. (5,6,13) Woolfenden et al (5) used cyclophosphamide and prednisone in their patient with PRS whose intravascular and cerebral findings responded well. Goldberg-Stern et al (6) used MTX and prednisolone in their patient and observed a decrease in the size of the enhanced area in the white matter. On review of PRS cases in the literature, we noted that some patients not receiving immunosuppression appear to have had progression of their PRS. (17-19)

This feature also seems to be true for LSCS. Stone et al (20) reported a patient with LSCS who responded well to immunosuppressive drugs, with regression of a cerebral lesion. An analysis of the literature revealed that LSCS patients who were not receiving immunosuppression did not have regression. (21)

[FIGURE 2 OMITTED]

Conclusion

This patient with PRS, who had immunoinflammatory findings similar to LSCS, benefitted in regard to cerebral involvement and immunomodulatory findings after receiving immunosuppressive treatment. These findings were established with MRI and laboratory evidence. We believe that PRS may be a clinical variant of LSCS, and immunosuppressive drugs might well be considered in the treatment of at least some eligible patients with PRS.

Acknowledgments

We thank our patient, who provided written consent for publication of his case.

References

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20. Stone J, Franks AJ, Guthrie JA, et al. Scleroderma 'en coup de sabre': pathological evidence of intracerebral inflammation. J Neurol Neurosurg Psychiatry 2001;70:382-385.

21. Gambichler T, Kreuter A, Hoffmann K, et al. Bilateral linear scleroderma 'en coup de sabre' associated with facial atrophy and neurological complications. BMC Dermatol 2001;1:9.

Cengiz Korkmaz, MD, Baki Adapinar, MD, and Seval Uysal, MD

From the Division of Rheumatology, Department of Internal Medicine and the Department of Radiology, Osmangazi University Medical Faculty, Eskisehir, Turkey; and the Neurology Department of Eskisehir State Hospital, Eskisehir, Turkey.

Reprint requests to Dr. Cengiz Korkmaz, Visnelik M. Alifuat Guven C, Akasya S. 11/11, 26020, Eskisehir, Turkiye. Email: [e-mail]

Accepted May 12, 2005.

The authors have no proprietary interest in any of the medications discussed in this article.

RELATED ARTICLE: Key Points

* Progressive facial hemiatrophy may have immunoinflammatory features similar to those of linear scleroderma en coup de sabre.

* Immunosuppressive drugs might well be considered in the treatment of at least some eligible patients with Parry-Romberg syndrome, especially in the case of cerebral involvement.