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Vasculitic neuropathy in chronic graft-versus-host disease (GVHD)
Journal of the Neurological Sciences 175 (2000) 71–72 www.elsevier.com / locate / jns
Letter to the Editor
Vasculitic neuropathy in chronic graft-versus-host disease (GVHD) Michael P. Collins*, M. Isabel Periquet The Ohio State University Medical Centre, Division of Neuromuscular Diseases, 1654 Upham Drive, Means Hall 4 th Floor, Columbus, OH 43210 -1228, USA Received 12 November 1999; accepted 18 November 1999
We read with interest the article on vasculitic neuropathy in chronic graft-versus-host disease (GVHD) by Gabriel et al. [1]. A case is reported of a patient with chronic myeloid leukemia who underwent an allogenic bone marrow transplant in 1989 and then developed chronic GVHD treated with prednisolone. Three years later, she started to develop patches of altered sensation on her distal limbs which slowly evolved over 4 years, unaccompanied by an exacerbation of the GVHD. When examined in 1996, she had multifocal pinprick loss with preserved reflexes and large-fiber sensory function. Electrical studies confirmed a multifocal sensory neuropathy (EMG not reported). Sural nerve biopsy showed asymmetric myelinated nerve fiber loss and mild endoneurial inflammation. One epineurial vessel was interpreted to show focal intimal proliferation and disruption of the internal elastic lamina (IEL). On this basis, vasculitic neuropathy was diagnosed but not treated (no change in steroid dose). The patient’s symptoms spontaneously resolved ‘2 years following onset of neuropathic symptoms.’ While the accompanying brief review of inflammatory neuropathies associated with GVHD is well done, the case itself is not convincing. Most importantly, the figures of the epineurial artery do not demonstrate vasculitis and show what appears to be a normal artery cut obliquely. There is no clear narrowing of the lumen as claimed. The lumen is circular in contour which is incompatible with asymmetric / focal intimal hyperplasia. The purported region of intimal thickening is 180 degrees opposed to the region of purported IEL disruption. These focal alterations should be adjacent to one another if truly a sign of healed vasculitis. On the other hand, the observed 180 degrees *Corresponding author. Tel.: 11-614-293-4981; fax: 11-614-2939029.
displacement is entirely consistent with oblique sectioning of a non-linear vessel. Staining for leukocytes, immune deposits, and hemosiderin might have been performed to support the vasculitis diagnosis, but were not reported. Moreover, inflammatory infiltrates in peripheral nervous system (PNS) vasculitis are almost always epineurial, not endoneurial [2]. There are other incongruities and atypical features to the case. (1) While the clinical examination showed preserved large-fiber sensory function in the distribution of the biopsied cutaneous nerve, the biopsy showed ‘moderate to marked’ focal depletion of myelinated nerve fibers. (2) Whereas only small-fiber sensory function (pinprick) was altered on examination, sensory loss in vasculitic neuropathies typically involves all modalities [3,4] and cutaneous biopsies reveal a predilection for large myelinated fiber involvement [5]. (3) No more than 10% of vasculitic neuropathies are purely or predominantly sensory (and even less if unrelated to rheumatoid arthritis, Sjogren’s syndrome, or HIV infection), as observed in this patient [2,4,6]. (4) Slowly evolving isolated / nonsystemic PNS vasculitis is, indeed, rarely reported [7], but most patients develop symptoms over weeks to months, not the 4 years encountered in this case. (5) With rare exceptions [8], vasculitic neuropathies do not spontaneously remit, as occurred in this patient. The authors do not explain why their patient was not treated for vasculitis. Whether vasculitic or not, it is difficult to ascribe an etiologic association between this patient’s neuropathy and her GVHD considering that (1) the neuropathy commenced 3 years after the onset of the GVHD, (2) the GVHD did not exacerbate in other tissues in coincidence with the peripheral nerve symptoms, and (3) no immunosuppressive interventions were made. Before GVHD is added to the growing list of systemic
0022-510X / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0022-510X( 00 )00283-5
72
M.P. Collins, M.I. Periquet / Journal of the Neurological Sciences 175 (2000) 71 – 72
conditions associated with vasculitis of the peripheral nerve, more persuasive cases will be required.
References [1] Gabriel CM, Goldman JM, Lucas S, Hughes RAC. Vasculitic neuropathy in association with chronic graft-versus-host disease. J Neurol Sci 1999;168:68–70. [2] Collins MP, Kissel JT, Mendell JR. Vasculitic neuropathies. In: Antel J, Birnbaum G, Hartung H-P, editors, Clinical neuroimmunology. Malden, MA: Blackwell Science, 1998:316–39. [3] Collins MP, Mendell JR, Periquet MI et al. Superficial peroneal nerve / peroneus brevis muscle biopsy in suspected vasculitic neuropathy: a cohort survey. Submitted to Neurology, 1999.
[4] Dyck PJ, Benstead TJ, Conn DL et al. Nonsystemic vasculitic neuropathy. Brain 1987;110:843–54. [5] Fujimura H, LaCroix C, Said G. Vulnerability of nerve fibers to ischaemia: a quantitative light and electron microscopic study. Brain 1991;114:1929–42. [6] Chia L, Fernandez A, LaCroix C, Adams D, Plante V, Said G. Contribution of nerve biopsy findings to the diagnosis of disabling neuropathy in the elderly: a retrospective review of 100 consecutive patients. Brain 1996;119:1091–8. [7] Kissel JT, Slivka AP, Warmolts JR, Mendell JR. The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. Ann Neurol 1985;18:251–7. [8] de la Sayette V, Macro M, Diraison P, Bertran F, Lechevalier B, Chapon F. Acute necrotizing vasculitis (polyarteritis nodosa?) confined to the nerve with spontaneous recovery. Br J Rheumatol 1995;34:694–5, Letter.
Letter to the Editor
Vasculitic neuropathy in chronic graft-versus-host disease (GVHD) Michael P. Collins*, M. Isabel Periquet The Ohio State University Medical Centre, Division of Neuromuscular Diseases, 1654 Upham Drive, Means Hall 4 th Floor, Columbus, OH 43210 -1228, USA Received 12 November 1999; accepted 18 November 1999
We read with interest the article on vasculitic neuropathy in chronic graft-versus-host disease (GVHD) by Gabriel et al. [1]. A case is reported of a patient with chronic myeloid leukemia who underwent an allogenic bone marrow transplant in 1989 and then developed chronic GVHD treated with prednisolone. Three years later, she started to develop patches of altered sensation on her distal limbs which slowly evolved over 4 years, unaccompanied by an exacerbation of the GVHD. When examined in 1996, she had multifocal pinprick loss with preserved reflexes and large-fiber sensory function. Electrical studies confirmed a multifocal sensory neuropathy (EMG not reported). Sural nerve biopsy showed asymmetric myelinated nerve fiber loss and mild endoneurial inflammation. One epineurial vessel was interpreted to show focal intimal proliferation and disruption of the internal elastic lamina (IEL). On this basis, vasculitic neuropathy was diagnosed but not treated (no change in steroid dose). The patient’s symptoms spontaneously resolved ‘2 years following onset of neuropathic symptoms.’ While the accompanying brief review of inflammatory neuropathies associated with GVHD is well done, the case itself is not convincing. Most importantly, the figures of the epineurial artery do not demonstrate vasculitis and show what appears to be a normal artery cut obliquely. There is no clear narrowing of the lumen as claimed. The lumen is circular in contour which is incompatible with asymmetric / focal intimal hyperplasia. The purported region of intimal thickening is 180 degrees opposed to the region of purported IEL disruption. These focal alterations should be adjacent to one another if truly a sign of healed vasculitis. On the other hand, the observed 180 degrees *Corresponding author. Tel.: 11-614-293-4981; fax: 11-614-2939029.
displacement is entirely consistent with oblique sectioning of a non-linear vessel. Staining for leukocytes, immune deposits, and hemosiderin might have been performed to support the vasculitis diagnosis, but were not reported. Moreover, inflammatory infiltrates in peripheral nervous system (PNS) vasculitis are almost always epineurial, not endoneurial [2]. There are other incongruities and atypical features to the case. (1) While the clinical examination showed preserved large-fiber sensory function in the distribution of the biopsied cutaneous nerve, the biopsy showed ‘moderate to marked’ focal depletion of myelinated nerve fibers. (2) Whereas only small-fiber sensory function (pinprick) was altered on examination, sensory loss in vasculitic neuropathies typically involves all modalities [3,4] and cutaneous biopsies reveal a predilection for large myelinated fiber involvement [5]. (3) No more than 10% of vasculitic neuropathies are purely or predominantly sensory (and even less if unrelated to rheumatoid arthritis, Sjogren’s syndrome, or HIV infection), as observed in this patient [2,4,6]. (4) Slowly evolving isolated / nonsystemic PNS vasculitis is, indeed, rarely reported [7], but most patients develop symptoms over weeks to months, not the 4 years encountered in this case. (5) With rare exceptions [8], vasculitic neuropathies do not spontaneously remit, as occurred in this patient. The authors do not explain why their patient was not treated for vasculitis. Whether vasculitic or not, it is difficult to ascribe an etiologic association between this patient’s neuropathy and her GVHD considering that (1) the neuropathy commenced 3 years after the onset of the GVHD, (2) the GVHD did not exacerbate in other tissues in coincidence with the peripheral nerve symptoms, and (3) no immunosuppressive interventions were made. Before GVHD is added to the growing list of systemic
0022-510X / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0022-510X( 00 )00283-5
72
M.P. Collins, M.I. Periquet / Journal of the Neurological Sciences 175 (2000) 71 – 72
conditions associated with vasculitis of the peripheral nerve, more persuasive cases will be required.
References [1] Gabriel CM, Goldman JM, Lucas S, Hughes RAC. Vasculitic neuropathy in association with chronic graft-versus-host disease. J Neurol Sci 1999;168:68–70. [2] Collins MP, Kissel JT, Mendell JR. Vasculitic neuropathies. In: Antel J, Birnbaum G, Hartung H-P, editors, Clinical neuroimmunology. Malden, MA: Blackwell Science, 1998:316–39. [3] Collins MP, Mendell JR, Periquet MI et al. Superficial peroneal nerve / peroneus brevis muscle biopsy in suspected vasculitic neuropathy: a cohort survey. Submitted to Neurology, 1999.
[4] Dyck PJ, Benstead TJ, Conn DL et al. Nonsystemic vasculitic neuropathy. Brain 1987;110:843–54. [5] Fujimura H, LaCroix C, Said G. Vulnerability of nerve fibers to ischaemia: a quantitative light and electron microscopic study. Brain 1991;114:1929–42. [6] Chia L, Fernandez A, LaCroix C, Adams D, Plante V, Said G. Contribution of nerve biopsy findings to the diagnosis of disabling neuropathy in the elderly: a retrospective review of 100 consecutive patients. Brain 1996;119:1091–8. [7] Kissel JT, Slivka AP, Warmolts JR, Mendell JR. The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. Ann Neurol 1985;18:251–7. [8] de la Sayette V, Macro M, Diraison P, Bertran F, Lechevalier B, Chapon F. Acute necrotizing vasculitis (polyarteritis nodosa?) confined to the nerve with spontaneous recovery. Br J Rheumatol 1995;34:694–5, Letter.