Case 35-2004: Nephrogenic Fibrosing Dermopathy
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《新英格兰医药杂志》
To the Editor: In Case 35-2004, Moschella et al. (Nov. 18 issue)1 discuss a patient with nephrogenic fibrosing dermopathy. There is growing evidence that the fibrosis may not be restricted to the skin but may be systemic, often involving the subcutaneous tissue, fascia, skeletal muscle, heart, lungs, and other organs.2,3,4 This evidence has led us to suggest an alternative name for this disorder — "dialysis-associated systemic fibrosis."3,4 Certain features of the patient discussed in the case suggest that skeletal muscle was involved: progressive weakness, an inability to walk, prominent flexion contractures over the elbows and knees, and the "woody induration" of the feet, which can also occur in the calf and quadriceps muscles.4 We believe a muscle biopsy would have shown endomysial or perimysial fibrosis, or both (Figure 1). We wish to emphasize the occurrence of a systemic fibrotic process in this disorder and to encourage a detailed and careful search for systemic involvement in similar patients.
Figure 1. Paraffin-Embedded Tissue Section (Mallory's Trichrome Stain).
A specimen of quadriceps muscle obtained at biopsy from a patient with a clinical presentation similar to that of the patient in Case 35-2004 shows excess blue staining around the muscle fibers, which is consistent with perimysial fibrosis.
Robert A. Taylor, M.D.
University of Iowa Hospitals and Clinics
Iowa City, IA 52242
Joshua M. Levine, M.D.
Massachusetts General Hospital
Boston, MA 02114
Sergio A. Jimenez, M.D.
Thomas Jefferson University
Philadelphia, PA 19107
sergio.jiminez@jefferson.edu
References
Case Records of the Massachusetts General Hospital (Case 35-2004). N Engl J Med 2004;351:2219-2227.
Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 2003;139:903-906.
Jimenez SA, Artlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 2004;50:2660-2666.
Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004;30:569-577.
To the Editor: A registry for nephrogenic fibrosing dermopathy lists more than 150 cases worldwide,1 and data from the registry suggest that a thrombotic complication often reveals unsuspected hypercoagulability and seems to trigger the nephrogenic fibrosing dermopathy.2 Along with fluid overload, hypoxemia and pleural effusions should prompt consideration of a pulmonary embolism in this setting.
Disease activity in nephrogenic fibrosing dermopathy seems to parallel worsening renal function (with a lag time of weeks to months). If renal function improves, nephrogenic fibrosing dermopathy tends to improve without any further skin-directed therapy. In the absence of controlled studies, claims of therapeutic efficacy in the setting of improving renal function should be treated with caution.
The authors claim that nephrogenic fibrosing dermopathy may follow "a short period of hemodialysis." Approximately 10 percent of cases of nephrogenic fibrosing dermopathy occur in patients who have never undergone dialysis. The implication that dialysis (by association) can cause nephrogenic fibrosing dermopathy is unfortunate, as evinced by several cases in which patients chose to stop dialysis — with fatal consequences.
Shawn E. Cowper, M.D.
Richard Bucala, M.D., Ph.D.
Yale University
New Haven, CT 06520
Philip E. LeBoit, M.D.
University of California, San Francisco
San Francisco, CA 94115
References
The International Center for Nephrogenic Fibrosing Dermopathy Research (ICNFDR) home page. (Accessed March 31, 2005, at http://www.icnfdr.org.)
Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 2003;15:785-790.
The authors reply: We agree with Taylor et al. that the patient's progressive weakness and inability to walk suggest skeletal-muscle involvement. At the time of this clinicopathological conference, skeletal-muscle involvement in nephrogenic fibrosing dermopathy had not yet been described.1
We also have observed an increased incidence of thrombotic complications among the cohort of patients with nephrogenic fibrosing dermopathy that is followed at the Massachusetts General Hospital. We agree with Cowper et al. that hypoxemia and pleural effusions should prompt consideration of pulmonary embolism. However, the resolution of this patient's hypoxemia, pleural effusions, and associated cough after dialysis — with a 17-kg reduction in his body weight — is consistent with fluid overload, not pulmonary embolism.
The patient in the Case Records had decreased firmness of his skin and increased range of motion of his knees with thalidomide treatment, in the setting of chronic renal failure that required hemodialysis, without improvement in his renal function. We agree with Cowper et al. that controlled studies of therapy for nephrogenic fibrosing dermopathy should be conducted and should consider changes in renal function.
We are aware that nephrogenic fibrosing dermopathy is a systemic disease that often presents with striking induration of the limbs and debilitating flexion contractures. In his discussion of the case, Dr. Moschella referred to an article by Ting et al. on systemic involvement in nephrogenic fibrosing dermopathy.2 He also pointed out that some of the initial 14 patients with nephrogenic fibrosing dermopathy reported in the study by Cowper et al. had not undergone hemodialysis.3 In his observations, Dr. Kay referred to "a short period of hemodialysis" in the context of contrasting the duration of renal failure preceding the onset of nephrogenic fibrosing dermopathy with that preceding the onset of 2-microglobulin amyloidosis, which typically appears after at least five years of dialysis treatment for chronic renal failure.4
Our only reservation about the comments of Taylor et al. is their suggested label of this entity as "dialysis-associated systemic fibrosis."5 Renaming this entity so as to imply that all cases are related to dialysis treatment would be inaccurate, as pointed out by Cowper et al., because nephrogenic fibrosing dermopathy has also developed in several patients who had renal insufficiency but who never underwent dialysis therapy.2 Thus, nephrogenic fibrosing dermopathy is associated more with the inadequately functioning kidney than with renal-replacement therapy.
Samuel L. Moschella, M.D.
Lahey Clinic
Burlington, MA 01805
Jonathan Kay, M.D.
Vincent Liu, M.D.
Massachusetts General Hospital
Boston, MA 02114
References
Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004;30:569-577.
Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 2003;139:903-906.
Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;356:1000-1001.
Kay J. 2-microglobulin amyloidosis. Int J Exp Clin Invest 1997;4:187-211.
Jimenez SA, Arlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 2004;50:2660-2666.
Figure 1. Paraffin-Embedded Tissue Section (Mallory's Trichrome Stain).
A specimen of quadriceps muscle obtained at biopsy from a patient with a clinical presentation similar to that of the patient in Case 35-2004 shows excess blue staining around the muscle fibers, which is consistent with perimysial fibrosis.
Robert A. Taylor, M.D.
University of Iowa Hospitals and Clinics
Iowa City, IA 52242
Joshua M. Levine, M.D.
Massachusetts General Hospital
Boston, MA 02114
Sergio A. Jimenez, M.D.
Thomas Jefferson University
Philadelphia, PA 19107
sergio.jiminez@jefferson.edu
References
Case Records of the Massachusetts General Hospital (Case 35-2004). N Engl J Med 2004;351:2219-2227.
Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 2003;139:903-906.
Jimenez SA, Artlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 2004;50:2660-2666.
Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004;30:569-577.
To the Editor: A registry for nephrogenic fibrosing dermopathy lists more than 150 cases worldwide,1 and data from the registry suggest that a thrombotic complication often reveals unsuspected hypercoagulability and seems to trigger the nephrogenic fibrosing dermopathy.2 Along with fluid overload, hypoxemia and pleural effusions should prompt consideration of a pulmonary embolism in this setting.
Disease activity in nephrogenic fibrosing dermopathy seems to parallel worsening renal function (with a lag time of weeks to months). If renal function improves, nephrogenic fibrosing dermopathy tends to improve without any further skin-directed therapy. In the absence of controlled studies, claims of therapeutic efficacy in the setting of improving renal function should be treated with caution.
The authors claim that nephrogenic fibrosing dermopathy may follow "a short period of hemodialysis." Approximately 10 percent of cases of nephrogenic fibrosing dermopathy occur in patients who have never undergone dialysis. The implication that dialysis (by association) can cause nephrogenic fibrosing dermopathy is unfortunate, as evinced by several cases in which patients chose to stop dialysis — with fatal consequences.
Shawn E. Cowper, M.D.
Richard Bucala, M.D., Ph.D.
Yale University
New Haven, CT 06520
Philip E. LeBoit, M.D.
University of California, San Francisco
San Francisco, CA 94115
References
The International Center for Nephrogenic Fibrosing Dermopathy Research (ICNFDR) home page. (Accessed March 31, 2005, at http://www.icnfdr.org.)
Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 2003;15:785-790.
The authors reply: We agree with Taylor et al. that the patient's progressive weakness and inability to walk suggest skeletal-muscle involvement. At the time of this clinicopathological conference, skeletal-muscle involvement in nephrogenic fibrosing dermopathy had not yet been described.1
We also have observed an increased incidence of thrombotic complications among the cohort of patients with nephrogenic fibrosing dermopathy that is followed at the Massachusetts General Hospital. We agree with Cowper et al. that hypoxemia and pleural effusions should prompt consideration of pulmonary embolism. However, the resolution of this patient's hypoxemia, pleural effusions, and associated cough after dialysis — with a 17-kg reduction in his body weight — is consistent with fluid overload, not pulmonary embolism.
The patient in the Case Records had decreased firmness of his skin and increased range of motion of his knees with thalidomide treatment, in the setting of chronic renal failure that required hemodialysis, without improvement in his renal function. We agree with Cowper et al. that controlled studies of therapy for nephrogenic fibrosing dermopathy should be conducted and should consider changes in renal function.
We are aware that nephrogenic fibrosing dermopathy is a systemic disease that often presents with striking induration of the limbs and debilitating flexion contractures. In his discussion of the case, Dr. Moschella referred to an article by Ting et al. on systemic involvement in nephrogenic fibrosing dermopathy.2 He also pointed out that some of the initial 14 patients with nephrogenic fibrosing dermopathy reported in the study by Cowper et al. had not undergone hemodialysis.3 In his observations, Dr. Kay referred to "a short period of hemodialysis" in the context of contrasting the duration of renal failure preceding the onset of nephrogenic fibrosing dermopathy with that preceding the onset of 2-microglobulin amyloidosis, which typically appears after at least five years of dialysis treatment for chronic renal failure.4
Our only reservation about the comments of Taylor et al. is their suggested label of this entity as "dialysis-associated systemic fibrosis."5 Renaming this entity so as to imply that all cases are related to dialysis treatment would be inaccurate, as pointed out by Cowper et al., because nephrogenic fibrosing dermopathy has also developed in several patients who had renal insufficiency but who never underwent dialysis therapy.2 Thus, nephrogenic fibrosing dermopathy is associated more with the inadequately functioning kidney than with renal-replacement therapy.
Samuel L. Moschella, M.D.
Lahey Clinic
Burlington, MA 01805
Jonathan Kay, M.D.
Vincent Liu, M.D.
Massachusetts General Hospital
Boston, MA 02114
References
Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004;30:569-577.
Ting WW, Stone MS, Madison KC, Kurtz K. Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 2003;139:903-906.
Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;356:1000-1001.
Kay J. 2-microglobulin amyloidosis. Int J Exp Clin Invest 1997;4:187-211.
Jimenez SA, Arlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 2004;50:2660-2666.