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|LETTERS TO EDITOR
|Year : 2016 | Volume
| Issue : 1 | Page : 157-159
Carbidopa-induced eosinophilic fasciitis: A review
Lucia Esteban-Fernandez1, Araceli Alonso-Canovas1, Luis Mariano Rojas-Medina2, Maria Asuncion Ballester-MartÍnez3, Inigo Corral-Corral1, Juan Carlos Martinez-Castrillo1
1 Department of Neurology, Ramon y Cajal University Hospital, Madrid, Spain
2 Department of Neurosurgery, Ramon y Cajal University Hospital, Madrid, Spain
3 Department of Dermatology, Ramon y Cajal University Hospital, Madrid, Spain
|Date of Web Publication||11-Jan-2016|
Department of Neurology, Ramon y Cajal University Hospital, Madrid
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Esteban-Fernandez L, Alonso-Canovas A, Rojas-Medina LM, Ballester-MartÍnez MA, Corral-Corral I, Martinez-Castrillo JC. Carbidopa-induced eosinophilic fasciitis: A review. Neurol India 2016;64:157-9
|How to cite this URL:|
Esteban-Fernandez L, Alonso-Canovas A, Rojas-Medina LM, Ballester-MartÍnez MA, Corral-Corral I, Martinez-Castrillo JC. Carbidopa-induced eosinophilic fasciitis: A review. Neurol India [serial online] 2016 [cited 2021 Sep 17];64:157-9. Available from: https://www.neurologyindia.com/text.asp?2016/64/1/157/173656
Carbidopa inhibits L-aromatic amino acid decarboxylase, a key enzyme in the synthesis of serotonin and dopamine. The combination of levodopa/carbidopa may frequently
cause nausea, hypotension, drowsiness, and dyskinesia.
Eosinophilic fasciitis (EF) is a rare immune-mediated disorder of unclear pathogenesis. More than 50% of the cases
are triggered by vigorous exercises or trauma. However, in a proportion of cases, no etiological factor may be identified.,,, Although many cases of sclerodermiform syndromes secondary to the combination 5-hydroxytryptophan/carbidopa have been reported, so far, carbidopa/levodopa administered without 5-hydroxytryptophan had not been linked to EF.,,, We report an extremely rare case of carbidopa-induced EF.
A 76-year-old man with a history of high blood pressure and prostatic cancer was treated with radiotherapy with a complete response 2 years ago. He was also a diagnosed case of Parkinson's disease for the past 6 years. He showed asymmetrical resting tremors, bradykinesia and mild axial involvement (Hoehn and Yahr stage II). Treatment with dopamine agonists (immediate-release pramipexole initially and prolonged-release ropirinole afterwards) improved his symptoms but caused lower limb swelling, which prompted the suspension of the drugs. Levodopa/carbidopa, 100/25 mg tid, had been started 5 years ago that had resulted in a favorable response. The dose was increased to 250/25 mg tid 3 years ago, and extended-release pramipexole, 2.1 mg qid, was added to optimize the motor control 2 years ago. It did not cause any relevant side effects. Levodopa/carbidopa was increased to 1000 mg per day to improve motor symptoms 2 weeks ago. The patient was admitted to our hospital with a history of painful, progressive increase in the waist circumference along with swelling of all four limbs for 6 weeks, with significant worsening when the doses of levodopa/carbidopa were increased. A dermatological examination revealed diffuse thickening of the skin and subcutaneous tissue, involving the upper and lower limbs, abdomen, and lower third of the chest, accompanied by intense xerosis in the lower limbs. His hands and feet were relatively spared. Subsequently, erythematous brownish plaques with ill-defined borders developed along the lines of skin tension on the abdominal wall and back, with a mild epidermal component in the inframammary folds [Figure 1]. Blood tests showed an eosinophilia (13.1%) of 900 cells/L (range, 0–600 cells/L), an increase in lactate dehydrogenase of 277 U/L (range, 115–221 U/L), and an erythrocyte sedimentation rate of 26 mm/h (range, 0–15 mm/h). The remaining blood count and biochemistry, serum immunoelectrophoresis, autoimmune disease tests, tumor markers, and serology for hepatitis viruses and Borrelia Burgdorferi were normal or negative. The thoracoabdominal computed tomographic (CT) scan and hepatic magnetic resonance imaging (MRI) showed small hepatic and biliary cysts, a hepatic hemangioma, and multinodular goiter; the gastrointestinal transit time was normal; the transthoracic echocardiogram showed slightly dilated right-sided cardiac cavities with preserved ejection fraction; and, nailfold capillaroscopy was normal. A deep skin biopsy that included the subcutaneous tissue and fascia, was performed on the right shoulder. Histologically, a moderate inflammatory infiltrate of lymphocytes and eosinophils was present in the fascia and deep part of the subcutaneous tissue [Figure 2]. Moreover, the deposition of mucin and collagen produced notable thickening of these tissues [Figure 3]. The findings confirmed the diagnosis of EF.
|Figure 1: Diffuse thickening of the skin with erythematous brownish plaques along the lines of skin tension of the abdominal wall and in the inframammary folds|
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|Figure 2: Inflammatory infiltrate located in the subcutaneous fat. The dermis is thickened by collagen deposition (H and E, ×25)|
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|Figure 3: The superficial fascia is markedly thickened, with sclerotic and mucinous change (H and E, ×100)|
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Suspecting carbidopa-induced EF, we withdrew the levodopa/carbidopa combination and started levodopa/benserazide, 200/50 mg qid, in association with prednisolone, 1 mg/kg (60 mg); the latter was progressively decreased in 2 weeks to 10 mg/day. In the first 2 weeks, the patient presented with a partial improvement. Hydroxychloroquine, 200 mg/day, was initiated in association with the corticosteroids; a remarkable improvement in the severity of skin lesions was evident approximately 5 days after the new therapy. The treatment was maintained for 1 month. Finally, after withdrawing the treatment, the patient remained asymptomatic during the follow-up period.
In our patient, the diagnosis of EF was confirmed by the clinical presentation and skin biopsy, as well as therapeutic response. and could, therefore, be differentiated from other sclerodermiform conditions  [Table 1]. A good response to drug withdrawal and corticosteroid therapy is typical. High-dose corticosteroid therapy is effective in 70% of the cases, and rarely, spontaneous remission may occur. In refractory or relapsing disease, such as in our case, immunomodulatory or immunosuppressive drugs may be indicated. We started hydroxychloroquine for three reasons: Its immunomodulatory effect, fewer side effects than immunosuppressants, and reported good results. Lakhanpal et al., in their series, reported satisfactory results in 62.5% of patients with EF treated with hydroxychloroquine alone.
|Table 1: Clinical differences between eosinophilic fasciitis and scleroderma|
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The history and laboratory tests ruled out known etiologies, including Borrelia Burgdorferi infection or treatment with other drugs previously associated with this disorder. It is highly unlikely that EF was related to his prostatic cancer, as the disease was well controlled; the association of EF and malignancy is very uncommon; and, the disease that is associated with cancer is typically refractory to corticosteroid therapy. Although EF has been associated with thyroid dysfunction, our patient had a simple goiter with normal thyroid stimulating hormone, thyroxine (T)4, and T3. The exacerbation of skin symptoms with increasing doses of carbidopa and his significant improvement after its discontinuation made it possible for us to establish a causal relationship between the drug and the EF. The long period of treatment with carbidopa before the onset of symptoms is not surprising either; in most of the reported drug-related cases of EF, it took approximately 20 months of treatment to develop clinical symptoms.,,
Several sclerodermiform conditions linked to the combination of 5-hydroxytryptophan/carbidopa have been reported.,,, The suspected mechanism is an increased bioavailability of 5-hydroxytryptophan, which is thought to be responsible for the sclerodermiform symptomatology, as proven with its exogenous administration., An abnormal immune response triggered by the drug seems a key phenomenon, as is seen in EF linked to phenytoin and lipid-lowering drugs., The mechanism by which carbidopa may cause EF is not clear. An increased bioavailability of endogenous tryptophan, along with an aberrant immune response, might be implicated.
We report the first case of carbidopa-induced EF, which underscores the need for eliciting a thorough history of the medications taken, and in maintaining a high index of suspicion while evaluating dermatological conditions typically associated with drugs. An early diagnosis and appropriate management may improve the long-term prognosis of the disease.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Bermejo Pareja F, Martinez-Martin P, Muradas V, de Yébenes JG. Carbidopa dosage modifies L-dopa induced side effects and blood levels of L-dopa and other amino acids in advanced Parkinsonism. Acta Neurol Scand 1985;72:506-11.
Naoui A, Bouslama K, Abdallah M, Hamzaoui S, Arbi T, Bahri F, et al
. Eosinophilic fasciitis (Shulman's disease): A case series of 11 patients. Rev Med Interne 2010;31:535-9.
Antic M, Lautenschlager S, Itin PH. Eosinophilic fasciitis 30 years after—What do we really know? Report of 11 patients and review of the literature. Dermatology 2006;213:93-101.
Bischoff L, Derk CT. Eosinophilic fasciitis: Demographics, disease pattern and response to treatment: Report of 12 cases and review of the literature. Int J Dermatol 2008;47:29-35.
Lakhanpal S, Ginsburg WW, Michet CJ, Doyle JA, Moore SB. Eosinophilic fasciitis: Clinical spectrum and therapeutic response in 52 cases. Semin Arthritis Rheum 1988;17:221-31.
Lampert A, Joly P, Thomine E, Ortoli JC, Lauret P. Scleroderma-like syndrome with bullous morphea during treatment with 5-hydroxytryptophan, carbidopa and flunitrazepam. Ann Dermatol Venereol 1992;119:209-11.
Auffranc JC, Berbis P, Fabre JC, Garnier JP, Privat Y. Sclerodermiform and poikilodermal syndrome observed during treatment with carbidopa and 5-hydroxytryptophan. Ann Dermatol Venereol 1985;112:691-2.
Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S, et al
. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980;303:782-7.
Joly P, Lampert A, Thomine E, Lauret P. Development of pseudobullous morphea and scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. J Am Acad Dermatol 1991;25:332-3.
Boin F, Hummers LK. Scleroderma-like fibrosing disorders. Rheum Dis Clin North Am 2008;34:199-220; ix.
Naschitz JE, Yeshurun D, Zuckerman E, Rosenbaum M, Misselevitch I, Shajrawi I, et al
. Cancer-associated fasciitis panniculitis. Cancer 1994;73:231-5.
Smiley AM, Husain M, Indenbaum S. Eosinophilic fasciitis in association with thyroid disease: A report of three cases. J Rheumatol 1980;7:871-6.
Smarius LJ, Jacobs GE, Hoeberechts-Lefrandt DH, de Kam ML, van der Post JP, de Rijk R, et al
. Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa. J Psychopharmacol 2008;22:426-33.
Buchanan RR, Gordon DA, Muckle TJ, McKenna F, Kraag G. The eosinophilic fasciitis syndrome after phenytoin (dilantin) therapy. J Rheumatol 1980;7:733-6.
Serrano-Grau P, Mascaró-Galy JM, Iranzo P. Eosinophilic fasciitis after taking simvastatin. Actas Dermosifiliogr 2008;99:420-1.
[Figure 1], [Figure 2], [Figure 3]
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