Journal of Dermatology 2014; 41: 266–283
LETTERS TO THE EDITOR
Cutaneous arteritis associated with peripheral neuropathy: Two case reports Dear Editor, Primary vasculitis confined to a single organ without systemic manifestation is referred to as single organ vasculitis (SOV).1 SOV that affects the skins or peripheral nerves has been named cutaneous arteritis or non-systemic vasculitic neuropathy (NSVN), respectively.1–3 These isolated vasculitides predominantly affect middle- or small-sized vessels within the lower dermis or epineurium and show relatively benign prognosis obtained by immunosuppressive therapies.2,3 We describe two cases of necrotizing vasculitis confined to the skin and peripheral nerves and discuss pathogenetic relationship between these isolated vasculitides. Case 1 was a 24-year-old woman who presented with sensory disturbance, progressive weakness, and pain in her hands
(a)
(f)
(b)
(g)
(c)
and feet, which had started 3 months prior. Chemical exposure, daily alcohol consumption and a history of diabetes mellitus were absent. On admission, the skin of the lower extremities demonstrated multiple livedo reticularis, purpura and tenderness (Fig. 1a–b). The weakness and sensory disturbance showed a pattern of mononeuritis multiplex predominantly in her left foot, which was supported by electrophysiological studies. Other constitutional symptoms were absent. Routine examinations of blood chemistry, urine and cerebrospinal fluid were normal. Tests for eosinophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), thiamine, anti-immunoglobulin (Ig)G cardiolipin, anti-IgG prothrombin, anti-SS-A/B, anti-DNA, anti-Sm, antineutrophil cytoplasmic antibodies, lupus anticoagulants, cryoglobulins,
(d)
(h)
(i)
(e)
(j)
Figure 1. Pathological findings of case 1 (a–h) and case 2 (i–j). In case 1, the surface of the lower extremities showed purpura (a) and livedo reticularis (b). A lower magnification view of a hematoxylin–eosin (HE)-stained biopsy specimen obtained from the purpura showed vasculitis affecting the small vessels in the subcutaneous panniculus (arrows) (c). Higher magnification revealed transmural infiltration (primarily of the lymphocytes) through the arteriolar wall (d). HE staining of an axial section of the sural nerve showed mononuclear cells infiltrating the epineurial arteriole and venule (e). Higher magnification revealed lymphocytic infiltration around the arteriole and fibrinoid necrosis of the vessel wall (f). A semi-thin, transverse epoxy section of the sural nerve stained with toluidine blue showed abundant myelin ovoids (g). A teased fiber of the sural nerve showed severe axonal degeneration (79%) without segmental demyelination (h). In case 2, a lower magnification view of a HE-stained biopsy specimen obtained from the purpura showed vasculitis affecting small vessels in the dermis-pannicular junction (arrow) (i). Higher magnification revealed marked lymphocytic and neutrophilic infiltration around the arteriole and fibrinoid necrosis of the arteriolar wall (j). Bars: (c,i) = 500 lm; (d) = 50 lm; (e) = 200 lm; (f,g,j) = 100 lm.
Correspondence: Gen Sobue, M.D., Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Email: [email protected]
266
© 2014 Japanese Dermatological Association
Letters to the Editor
angiotensin-converting enzyme, IgE, complement, and soluble interleukin-2 receptor and serum immunoelectrophoresis showed normal results. Serum markers for hepatitis viruses and syphilis were negative. Radiological procedures revealed no stenosis of the major vessels. A skin and sural nerve biopsy specimen revealed necrotizing vasculitis primarily involving the arterioles, venules and capillaries within the lower dermis and epineurium (Fig. 1c–f), and severe axonal degeneration (Fig. 1g–h). Daily i.v. administration of methylprednisolone (1 g/day 9 3 days) and subsequent tapering produced a marked clinical improvement, while minimal weakness and brownish pigmentation of her feet remained. Case 2 was a 74-year-old woman presenting with livedo reticularis, thumb-sized purpura, tenderness and edema in her lower extremities accompanied by a tingling sensation and weakness with a pattern of polyneuropathy. She sometimes experienced general fatigue and fever up to 38°C but lacked other constitutional symptoms. ESR and CRP were 98 mm/h and 13.5 mg/dL, respectively, and rheumatoid factor (RF) was positive, but the other results were normal, as with case 1. A skin biopsy specimen revealed necrotizing vasculitis within the lower dermis (Fig. 1i–j). Daily oral prednisolone (1 mg/kg per day) for 2 weeks and subsequent tapering produced marked clinical improvement. The clinicopathological phenotypes of our cases overlapped with features of cutaneous arteritis and peripheral neuropathy. Particularly, case 1 showed vasculitis in both skin and nerve biopsy specimens. Positive RF, elevation of ESR or fever seen in case 2 may be found in cutaneous arteritis or NSVN.2–4 The current diagnostic criteria for NSVN exclude the involvement of extraneural tissues, including the skin.4 In contrast, peripheral neuropathy has been described as a compli-
cation of cutaneous arteritis, whereas there have been few definite case reports.5 Considering the clinicopathological results of our cases, cutaneous arteritis and NSVN may not be entirely tissue-specific entities but included in a continuous disease spectrum that can affect the skin and peripheral nerves.
CONFLICT OF INTEREST:
None.
Yuichi RIKU, Kensuke IKENAKA, Haruki KOIKE, Yoshiki NIIMI, Jo SENDA, Rina HASHIMOTO, Yuichi KAWAGASHIRA, Minoru TOMITA, Masahiro IIJIMA, Gen SOBUE Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan doi: 10.1111/1346-8138.12416
REFERENCES 1 Jenette JC, Falk RJ, Bacon PA et al. 2012 Revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013; 65: 1–11. 2 Moreland LW, Ball GV. Cutaneous polyarteritis nodosa. Am J Med 1990; 88: 426–430. 3 Dyck PJ, Benstead TJ, Conn DL, Stevens JC, Windebank AJ, Low PA. Nonsystemic vasculitic neuropathy. Brain 1987; 110: 843–853. 4 Collins MP, Dyck PJ, Gronseth GS et al. Peripheral nerve society guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: executive summary. J Peripher Nerv Syst 2010; 15: 176–184. 5 Satoh J, Yamamoto T, Kuroda Y. Vasculitis confined to the peripheral nerve and skin: a variant of non-systemic vasculitic neuropathy. Eur J Neurol 1999; 6: 241–244.
Etanercept-induced sarcoidosis presented with scrotal lesion: A rare manifestation in genital area Dear Editor Tumor necrosis factor-a antagonists have been widely used in various inflammatory diseases such as psoriasis, psoriatic arthritis, rheumatoid arthritis and spondyloarthropathy.1 Nevertheless, one of the side-effects of TNF-a antagonists is sarcoidosis-like granulomatosis. Among TNF-a antagonists, etanercept is commonly reported.1 Herein, we report a case of etanercept-induced sarcoidosis presenting with a lesion on the scrotum. A 50-year-old man presented with asymptomatic erythematous annular plaques on the scrotum for 1 month (Fig. 1a,c). He had underlying disease of undifferentiated seronegative spondyloarthropathy. In August 2010, the disease flared up with low back pain, polyarthritis, enthesitis and uveitis, and he
was treated with sulfasalazine, methotrexate, leflunomide and non-steroidal anti-inflammatory drugs. He still had arthritis and a high erythrocyte sedimentary rate. Etanercept 50 mg via s.c. injection once a week was started in May 2011. One month after treatment, arthritis was improved. In August 2011, he developed skin lesions. He denied fever, cough, weight loss and history of tuberculosis exposure. Dermatological examination revealed few indurated erythematous annular plaques at the scrotum. Skin biopsy showed non-caseating epithelioid granulomas surrounded with pauci-lymphocytic infiltration (Fig. 1b,d). Foreign bodies and acid-fast bacilli were not found. Tissue cultures for mycobacteria and fungus were negative. Laboratory investigation showed that chest radiography had changed from normal to mild interstitial thickening at the right
Correspondence: Narumol Silpa-archa, M.D., Department of Dermatology, Siriraj Hospital, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand. Email: [email protected]
© 2014 Japanese Dermatological Association
267
LETTERS TO THE EDITOR
Cutaneous arteritis associated with peripheral neuropathy: Two case reports Dear Editor, Primary vasculitis confined to a single organ without systemic manifestation is referred to as single organ vasculitis (SOV).1 SOV that affects the skins or peripheral nerves has been named cutaneous arteritis or non-systemic vasculitic neuropathy (NSVN), respectively.1–3 These isolated vasculitides predominantly affect middle- or small-sized vessels within the lower dermis or epineurium and show relatively benign prognosis obtained by immunosuppressive therapies.2,3 We describe two cases of necrotizing vasculitis confined to the skin and peripheral nerves and discuss pathogenetic relationship between these isolated vasculitides. Case 1 was a 24-year-old woman who presented with sensory disturbance, progressive weakness, and pain in her hands
(a)
(f)
(b)
(g)
(c)
and feet, which had started 3 months prior. Chemical exposure, daily alcohol consumption and a history of diabetes mellitus were absent. On admission, the skin of the lower extremities demonstrated multiple livedo reticularis, purpura and tenderness (Fig. 1a–b). The weakness and sensory disturbance showed a pattern of mononeuritis multiplex predominantly in her left foot, which was supported by electrophysiological studies. Other constitutional symptoms were absent. Routine examinations of blood chemistry, urine and cerebrospinal fluid were normal. Tests for eosinophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), thiamine, anti-immunoglobulin (Ig)G cardiolipin, anti-IgG prothrombin, anti-SS-A/B, anti-DNA, anti-Sm, antineutrophil cytoplasmic antibodies, lupus anticoagulants, cryoglobulins,
(d)
(h)
(i)
(e)
(j)
Figure 1. Pathological findings of case 1 (a–h) and case 2 (i–j). In case 1, the surface of the lower extremities showed purpura (a) and livedo reticularis (b). A lower magnification view of a hematoxylin–eosin (HE)-stained biopsy specimen obtained from the purpura showed vasculitis affecting the small vessels in the subcutaneous panniculus (arrows) (c). Higher magnification revealed transmural infiltration (primarily of the lymphocytes) through the arteriolar wall (d). HE staining of an axial section of the sural nerve showed mononuclear cells infiltrating the epineurial arteriole and venule (e). Higher magnification revealed lymphocytic infiltration around the arteriole and fibrinoid necrosis of the vessel wall (f). A semi-thin, transverse epoxy section of the sural nerve stained with toluidine blue showed abundant myelin ovoids (g). A teased fiber of the sural nerve showed severe axonal degeneration (79%) without segmental demyelination (h). In case 2, a lower magnification view of a HE-stained biopsy specimen obtained from the purpura showed vasculitis affecting small vessels in the dermis-pannicular junction (arrow) (i). Higher magnification revealed marked lymphocytic and neutrophilic infiltration around the arteriole and fibrinoid necrosis of the arteriolar wall (j). Bars: (c,i) = 500 lm; (d) = 50 lm; (e) = 200 lm; (f,g,j) = 100 lm.
Correspondence: Gen Sobue, M.D., Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Email: [email protected]
266
© 2014 Japanese Dermatological Association
Letters to the Editor
angiotensin-converting enzyme, IgE, complement, and soluble interleukin-2 receptor and serum immunoelectrophoresis showed normal results. Serum markers for hepatitis viruses and syphilis were negative. Radiological procedures revealed no stenosis of the major vessels. A skin and sural nerve biopsy specimen revealed necrotizing vasculitis primarily involving the arterioles, venules and capillaries within the lower dermis and epineurium (Fig. 1c–f), and severe axonal degeneration (Fig. 1g–h). Daily i.v. administration of methylprednisolone (1 g/day 9 3 days) and subsequent tapering produced a marked clinical improvement, while minimal weakness and brownish pigmentation of her feet remained. Case 2 was a 74-year-old woman presenting with livedo reticularis, thumb-sized purpura, tenderness and edema in her lower extremities accompanied by a tingling sensation and weakness with a pattern of polyneuropathy. She sometimes experienced general fatigue and fever up to 38°C but lacked other constitutional symptoms. ESR and CRP were 98 mm/h and 13.5 mg/dL, respectively, and rheumatoid factor (RF) was positive, but the other results were normal, as with case 1. A skin biopsy specimen revealed necrotizing vasculitis within the lower dermis (Fig. 1i–j). Daily oral prednisolone (1 mg/kg per day) for 2 weeks and subsequent tapering produced marked clinical improvement. The clinicopathological phenotypes of our cases overlapped with features of cutaneous arteritis and peripheral neuropathy. Particularly, case 1 showed vasculitis in both skin and nerve biopsy specimens. Positive RF, elevation of ESR or fever seen in case 2 may be found in cutaneous arteritis or NSVN.2–4 The current diagnostic criteria for NSVN exclude the involvement of extraneural tissues, including the skin.4 In contrast, peripheral neuropathy has been described as a compli-
cation of cutaneous arteritis, whereas there have been few definite case reports.5 Considering the clinicopathological results of our cases, cutaneous arteritis and NSVN may not be entirely tissue-specific entities but included in a continuous disease spectrum that can affect the skin and peripheral nerves.
CONFLICT OF INTEREST:
None.
Yuichi RIKU, Kensuke IKENAKA, Haruki KOIKE, Yoshiki NIIMI, Jo SENDA, Rina HASHIMOTO, Yuichi KAWAGASHIRA, Minoru TOMITA, Masahiro IIJIMA, Gen SOBUE Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan doi: 10.1111/1346-8138.12416
REFERENCES 1 Jenette JC, Falk RJ, Bacon PA et al. 2012 Revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013; 65: 1–11. 2 Moreland LW, Ball GV. Cutaneous polyarteritis nodosa. Am J Med 1990; 88: 426–430. 3 Dyck PJ, Benstead TJ, Conn DL, Stevens JC, Windebank AJ, Low PA. Nonsystemic vasculitic neuropathy. Brain 1987; 110: 843–853. 4 Collins MP, Dyck PJ, Gronseth GS et al. Peripheral nerve society guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: executive summary. J Peripher Nerv Syst 2010; 15: 176–184. 5 Satoh J, Yamamoto T, Kuroda Y. Vasculitis confined to the peripheral nerve and skin: a variant of non-systemic vasculitic neuropathy. Eur J Neurol 1999; 6: 241–244.
Etanercept-induced sarcoidosis presented with scrotal lesion: A rare manifestation in genital area Dear Editor Tumor necrosis factor-a antagonists have been widely used in various inflammatory diseases such as psoriasis, psoriatic arthritis, rheumatoid arthritis and spondyloarthropathy.1 Nevertheless, one of the side-effects of TNF-a antagonists is sarcoidosis-like granulomatosis. Among TNF-a antagonists, etanercept is commonly reported.1 Herein, we report a case of etanercept-induced sarcoidosis presenting with a lesion on the scrotum. A 50-year-old man presented with asymptomatic erythematous annular plaques on the scrotum for 1 month (Fig. 1a,c). He had underlying disease of undifferentiated seronegative spondyloarthropathy. In August 2010, the disease flared up with low back pain, polyarthritis, enthesitis and uveitis, and he
was treated with sulfasalazine, methotrexate, leflunomide and non-steroidal anti-inflammatory drugs. He still had arthritis and a high erythrocyte sedimentary rate. Etanercept 50 mg via s.c. injection once a week was started in May 2011. One month after treatment, arthritis was improved. In August 2011, he developed skin lesions. He denied fever, cough, weight loss and history of tuberculosis exposure. Dermatological examination revealed few indurated erythematous annular plaques at the scrotum. Skin biopsy showed non-caseating epithelioid granulomas surrounded with pauci-lymphocytic infiltration (Fig. 1b,d). Foreign bodies and acid-fast bacilli were not found. Tissue cultures for mycobacteria and fungus were negative. Laboratory investigation showed that chest radiography had changed from normal to mild interstitial thickening at the right
Correspondence: Narumol Silpa-archa, M.D., Department of Dermatology, Siriraj Hospital, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand. Email: [email protected]
© 2014 Japanese Dermatological Association
267
