CASE REPORT
POEMS Syndrome Complicated by Extensive Calciphylaxis: A Remarkable Recovery Emilie Bourgeault, Alice Dahl, Marie-Marthe Thibeault, Audrey Dupe´re´, Anne-Marie Drolet, and Jean Mathieu Background and Objective: Calciphylaxis is life threatening. It has traditionally been associated with end-stage renal disease and hyperparathyroidism but is increasingly common in other clinical contexts. The association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and calciphylaxis has been reported only in a few cases. This case is the first of patient survival in such widespread disease. Methods and Results: A 42-year-old man with POEMS syndrome developed extensive calciphylaxis despite normal renal and parathyroid function. Rapid diagnosis, treatment, and supportive care contributed to full clinical resolution. Conclusion: This is the fifth case of POEMS syndrome associated with calciphylaxis. The observations from this report suggest that POEMS syndrome might be an independent risk factor for the development of calciphylaxis. This case underlines the importance of careful follow-up in patients with POEMS syndrome and prompt diagnosis and treatment of associated calciphylaxis. Contexte et objectif: La calciphylaxie est une maladie potentiellement mortelle. Elle est habituellement associe´e a` une insuffisance re´nale terminale ou a` l’hyperparathyroidie, mais elle s’observe de plus en plus souvent dans d’autres contextes cliniques. La pre´sence concomitante de polyneuropathie, d’organome´galie, d’endocrinopathie, de gammopathie monoclonale et de signes cutane´s, connue sous le nom de syndrome POEMS (acronyme anglais), et de calciphylaxie n’est mentionne´e que dans quelques expose´s de cas. Suit la description du premier cas de survie a` une atteinte tre`s e´tendue. Me´thode et re´sultats: Un homme de 42 ans, atteint du syndrome POEMS a commence´ a` pre´senter des signes de calciphylaxie e´tendue, et ce, malgre´ un fonctionnement normal des reins et des parathyroı¨des. La pose pre´coce du diagnostic et une mise en route rapide du traitement ainsi des soins de soutien sont tous des e´le´ments qui ont contribue´ a` une gue´rison comple`te sur le plan clinique. Conclusions: Il s’agit du cinquie`me cas de syndrome POEMS associe´ a` la calciphylaxie. Les observations tire´es de l’expose´ de cas laissent supposer que le syndrome POEMS peut se re´ve´ler un facteur de risque inde´pendant de calciphylaxie. Le cas de´crit ici fait ressortir l’importance d’un suivi me´ticuleux chez les patients atteints du syndrome POEMS, de meˆme que de la pose pre´coce du diagnostic et de la mise en route rapide du traitement de la calciphylaxie concomitante.
OLYNEUROPATHY, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare paraneoplastic syndrome.1 The diagnostic criteria include a constellation of cutaneous findings, and as such, the dermatologist plays an imperative role in the recognition and diagnosis of this entity. Calciphylaxis is a rare, life-threatening condition that involves vascular calcification and tissue necrosis. It has been traditionally described in patients with end-stage
P
Address reprint requests to: Emilie Bourgeault, MD, Hoˆtel-Dieu de Que´bec, Division of Dermatology, Laval University, 11 Coˆte du Palais, Que´bec, QC G1R 2J6; e-mail: [email protected].
DOI 10.2310/7750.2014.14086 # 2014 Canadian Dermatology Association
renal disease but can also be observed in nonuremic patients.2,3 Four cases of POEMS syndrome associated with calciphylaxis have been reported.4–7 We present a fifth case of POEMS syndrome and calciphylaxis. To our knowledge, this case is the first of patient survival in such widespread disease.
Report of a Case A 42-year-old man was diagnosed with chronic inflammatory demyelinating polyradiculopathy in January 2010. He was unresponsive to a number of treatments, including systemic steroids, intravenous immunoglobulin, and rituximab. In the summer of 2011, he was hospitalized due to deterioration of his condition, which involved profound weight loss and a decline in his neurologic state.
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
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Bourgeault et al
During his hospital stay, he was seen in Dermatology for many skin changes, including diffuse hyperpigmentation, hypertrichosis, ichthyosis, clubbing, lower extremity edema, and hyperhidrosis. He also had numerous erythematous macules and papules on the trunk and proximal limbs that were compatible with multiple glomeruloid hemangiomas and cherry hemangiomas confirmed by biopsy. Serum immunoelectrophoresis/ immunofixation electrophoresis revealed an IgG lambda monoclonal gammopathy. Two bone marrow aspirations and biopsies were negative. A computed tomographic scan showed blastic and lytic lesions in the spine. Further laboratory examination of endocrine function revealed hypothyroidism, hypogonadism, and adrenal insufficiency. These findings led to the diagnosis of POEMS syndrome. He was treated by chemotherapy using melphalan and prednisone for three cycles but failed to respond. He then received cyclophosphamide and dexamethasone, again without clinical response. Later, the patient was seen in Dermatology for a sudden widespread eruption of violaceous plaques with irregular borders on his trunk and proximal extremities along with overall clinical deterioration. A skin biopsy obtained from a plaque on his left thigh showed microthrombi and widespread calcification of the small- to medium-sized blood vessels, typical of calciphylaxis (Figure 1). Laboratory examinations including complete blood count, renal and liver function, electrolytes including calcium, parathyroid hormone (PTH) levels, and autoimmune parameters were normal. The skin lesions quickly worsened into widespread necrotic and painful ulcers (Figure 2). He was transferred to a tertiary care center, and the calciphylaxis was treated with etidronate disodium and intravenous sodium thiosulfate. Bone lesions were treated by radiotherapy. A trial of bortezomib led to severe pain
Figure 1. Calcification of a small vessel in the panniculus (hematoxylineosin stain; original magnification 3 100).
2
Figure 2. Large retiform ulceration with eschar of the right suprapubic area surrounded by violaceous, indurated, tender, retiform plaques.
and violaceous discoloration of limbs. This medication was discontinued after three doses. Overall, the evolution was favorable despite widespread calciphylaxis with necrotic ulcers that were treated with split-thickness skin grafts and weekly intravenous sodium thiosulfate. Since his discharge from hospital and resolution of cutaneous ulcers, lenalidomide has been initiated, with significant results. The patient has residual distal neuropathic changes, but, otherwise, he completely recovered.
Discussion POEMS syndrome is a rare paraneoplastic disorder associated with an underlying plasma cell dyscrasia. To make a diagnosis, the major criteria of polyneuropathy and monoclonal plasmaproliferative disorder must be present. At least one of the minor criteria, excluding diabetes or thyroid abnormalities, must also be present: sclerotic bone lesions, Castleman disease, organomegaly, volume overload, endocrinopathy, skin changes, and papilledema.8 Other symptoms often associated with the syndrome include weight loss, fever, pulmonary function test abnormalities, fatigue, and diarrhea.9,10 Cutaneous manifestations, although generally nonspecific, have been shown to occur in 90% of patients with POEMS syndrome.10 Cutaneous findings include hyperpigmentation, hemangiomas, hypertrichosis, leukonychia, nail clubbing, sclerodermoid changes, and vascular skin changes such as Raynaud phenomenon, hyperemia/ erythema, flushing, rubor, acrocyanosis, and vasculitis, with patients reported as having a mean of three findings
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
POEMS Syndrome Complicated by Extensive Calciphylaxis
at diagnosis.10,11 The most common skin findings include hyperpigmentation and hemangiomas.10 The hyperpigmentation, which is seen in over 90% of patients,11 is usually generalized but can also have an acral or truncal distribution.10 Multiple hemangiomas, including cherry, lobular, and glomeruloid, are seen in up to 47% of patients,10 with the glomeruloid subtype considered to be a specific marker of the syndrome.12 Multiple theories have been proposed regarding the pathophysiology of skin changes seen in POEMS. Levels of vascular endothelial growth factor (VEGF) are elevated in patients with POEMS syndrome and seem to correlate with disease activity.12 It is plausible that the VEGF plays a role in the development of the cutaneous changes10; however, the relationship is not clear, and other possible etiologies, such as direct infiltration of malignant plasma cells, may also contribute to the observed skin changes.12 Cutaneous calciphylaxis is a severe microvascular occlusion disorder with a mortality rate of up to 89%.13 The disorder involves mural calcification, intimal proliferation, fibrosis, and thrombosis leading to painful lesions of noninflammatory retiform purpura and subsequent necrotic ulcerations.14 Numerous risk factors have been identified in the development of calciphylaxis, including renal failure, diabetes mellitus, hypoalbuminemia, obesity, liver disease, malignant neoplasm, chemotherapy, systemic inflammation, hepatic cirrhosis, protein C or S deficiency, rapid weight loss, infection, systemic glucocorticoid use, anticoagulation with warfarin, abnormalities in the calciumphosphate axis, and elevated serum aluminium.14,15 Hypercalcemia is a frequent finding in several neoplasms, especially in multiple myeloma; however, vascular calcification and calciphylaxis in association with neoplasia is a rare occurrence.15 Other than the paraneoplastic syndrome, our patient did not have any predisposing risk factors for this disorder. The pathogenesis underlying vascular calcification in calciphylaxis is complex and ultimately involves activation of the nuclear factor kB (NF-kB) pathway.15 The relative importance of the multiple factors leading to the calcium deposition is unclear, and most treatments thus far have focused on the calcium-phosphate-PTH axis, with successful results even in cases with no documented renal or parathyroid dysfunction.13 Although vascular calcification is the main element in calciphylaxis, the three components of the Virchow triad, including reduced blood flow, vascular endothelial injury, and hypercoagulability, are seemingly at the root of the disease, leading to the extensive ischemic necrosis observed.15
The mean survival after diagnosis of POEMS syndrome ranges from 8 to 13 years.11 However, up to 50% of patients with calciphylaxis die within 1 year of diagnosis, mainly due to sepsis.15 Proximal involvement of calciphylaxis, as in our case, has been associated with a poorer prognosis.3 We believe that our patient’s remarkable recovery is due to intense wound care and to the prompt initiation of treatment with a bisphosphonate and sodium thiosulfate, even in the context of a normal calciumphosphate axis. The impressive and sustained clinical improvement was also attributed to lenalidomide, which treated the underlying plasma cell dyscrasia. This case emphasizes that POEMS syndrome is a significant risk factor for calciphylaxis. Dermatologists should be aware of this possibility when following patients with the syndrome. Timely diagnosis is imperative with regard to prognosis. Our case clearly demonstrates that a favorable patient outcome is possible.
Acknowledgments Eric Gagne´, MD, kindly provided dermatopathology assistance. Financial disclosure of authors and reviewers: None reported.
References 1. Dispenzieri A, Buadi FK. A review of POEMS syndrome. Oncology (Williston Park) 2013;27:1242–50. 2. Stanciu M, Gagne´-Henley A, The´rien G. Unusual case of proximal calciphylaxis without renal failure. J Cutan Med Surg 2011;15:290–2. 3. Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis. J Am Acad Dermatol 2011;65:1–12, doi:10.1016/j.jaad.2010.08.038. 4. Hineno A, Kinoshita T, Kinoshita M, et al. Calciphylaxis as a catastrophic complication in a patient with POEMS syndrome. Case Rep Neurol 2009;1:47–53, doi:10.1159/000259906. 5. Lee FY, Chiu HC. POEMS syndrome with calciphylaxis: a case report. Acta Derm Venereol 2011;91:96–7, doi:10.2340/00015555-0986. 6. Yoshikawa M, Uhara H, Arakura F, et al. Calciphylaxis in POEMS syndrome: a case treated with etidronate. Acta Derm Venereol 2011;91:98–9. 7. De Roma I, Filotico R, Cea M, et al. Calciphylaxis in a patient with POEMS syndrome without renal failure and/or hyperparathyroidism. A case report. Ann Ital Med Int 2004;19:283–7. 8. Dispenzieri A, Kyle RA, Lacy MQ, et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101:2496–506, doi:10.1182/blood-2002-07-2299. 9. Miest RY, Comfere NI, Dispenzieri A, et al. Cutaneous manifestations in patients with POEMS syndrome. Int J Dermatol 2013;52: 1349–56, doi:10.1111/j.1365-4632.2012.05648.x. 10. Phillips JA, Dixon JE, Richardson JB, et al. Glomeruloid hemangioma leading to a diagnosis of POEMS syndrome. J Am Acad Dermatol 2006;55:149–52, doi:10.1016/j.jaad.2006.02.036.
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
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Bourgeault et al
11. Colaco SM, Miller T, Ruben BS, et al. IgM-lambda paraproteinemia with associated cutaneous lymphoplasmacytic infiltrate in a patient who meets diagnostic criteria for POEMS syndrome. J Am Acad Dermatol 2008;58:671–5, doi:10.1016/j.jaad.2007.07.021. 12. D’Souza A, Hayman SR, Buadi F, et al. The utility of plasma vascular endothelial growth factor levels in the diagnosis of POEMS syndrome. Blood 2011;118:4663–5, doi:10.1182/blood2011-06-362392.
4
13. Kalajian AH, Malhotra PS, Callen JP, Parker LP. Calciphylaxis with normal renal and parathyroid function: not as rare as previously believed. Arch Dermatol 2009;145:451–8. 14. Weenig RH. Pathogenesis of calciphylaxis: Hans Selye to nuclear factor k-B. J Am Acad Dermatol 2008;58:458–71, doi:10.1016/ j.jaad.2007.12.006. 15. Alain J, Poulin YP, Cloutier RA, et al. Calciphylaxis: seven new cases. J Cutan Med Surg 2000;4:213–8.
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
POEMS Syndrome Complicated by Extensive Calciphylaxis: A Remarkable Recovery Emilie Bourgeault, Alice Dahl, Marie-Marthe Thibeault, Audrey Dupe´re´, Anne-Marie Drolet, and Jean Mathieu Background and Objective: Calciphylaxis is life threatening. It has traditionally been associated with end-stage renal disease and hyperparathyroidism but is increasingly common in other clinical contexts. The association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and calciphylaxis has been reported only in a few cases. This case is the first of patient survival in such widespread disease. Methods and Results: A 42-year-old man with POEMS syndrome developed extensive calciphylaxis despite normal renal and parathyroid function. Rapid diagnosis, treatment, and supportive care contributed to full clinical resolution. Conclusion: This is the fifth case of POEMS syndrome associated with calciphylaxis. The observations from this report suggest that POEMS syndrome might be an independent risk factor for the development of calciphylaxis. This case underlines the importance of careful follow-up in patients with POEMS syndrome and prompt diagnosis and treatment of associated calciphylaxis. Contexte et objectif: La calciphylaxie est une maladie potentiellement mortelle. Elle est habituellement associe´e a` une insuffisance re´nale terminale ou a` l’hyperparathyroidie, mais elle s’observe de plus en plus souvent dans d’autres contextes cliniques. La pre´sence concomitante de polyneuropathie, d’organome´galie, d’endocrinopathie, de gammopathie monoclonale et de signes cutane´s, connue sous le nom de syndrome POEMS (acronyme anglais), et de calciphylaxie n’est mentionne´e que dans quelques expose´s de cas. Suit la description du premier cas de survie a` une atteinte tre`s e´tendue. Me´thode et re´sultats: Un homme de 42 ans, atteint du syndrome POEMS a commence´ a` pre´senter des signes de calciphylaxie e´tendue, et ce, malgre´ un fonctionnement normal des reins et des parathyroı¨des. La pose pre´coce du diagnostic et une mise en route rapide du traitement ainsi des soins de soutien sont tous des e´le´ments qui ont contribue´ a` une gue´rison comple`te sur le plan clinique. Conclusions: Il s’agit du cinquie`me cas de syndrome POEMS associe´ a` la calciphylaxie. Les observations tire´es de l’expose´ de cas laissent supposer que le syndrome POEMS peut se re´ve´ler un facteur de risque inde´pendant de calciphylaxie. Le cas de´crit ici fait ressortir l’importance d’un suivi me´ticuleux chez les patients atteints du syndrome POEMS, de meˆme que de la pose pre´coce du diagnostic et de la mise en route rapide du traitement de la calciphylaxie concomitante.
OLYNEUROPATHY, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare paraneoplastic syndrome.1 The diagnostic criteria include a constellation of cutaneous findings, and as such, the dermatologist plays an imperative role in the recognition and diagnosis of this entity. Calciphylaxis is a rare, life-threatening condition that involves vascular calcification and tissue necrosis. It has been traditionally described in patients with end-stage
P
Address reprint requests to: Emilie Bourgeault, MD, Hoˆtel-Dieu de Que´bec, Division of Dermatology, Laval University, 11 Coˆte du Palais, Que´bec, QC G1R 2J6; e-mail: [email protected].
DOI 10.2310/7750.2014.14086 # 2014 Canadian Dermatology Association
renal disease but can also be observed in nonuremic patients.2,3 Four cases of POEMS syndrome associated with calciphylaxis have been reported.4–7 We present a fifth case of POEMS syndrome and calciphylaxis. To our knowledge, this case is the first of patient survival in such widespread disease.
Report of a Case A 42-year-old man was diagnosed with chronic inflammatory demyelinating polyradiculopathy in January 2010. He was unresponsive to a number of treatments, including systemic steroids, intravenous immunoglobulin, and rituximab. In the summer of 2011, he was hospitalized due to deterioration of his condition, which involved profound weight loss and a decline in his neurologic state.
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
1
Bourgeault et al
During his hospital stay, he was seen in Dermatology for many skin changes, including diffuse hyperpigmentation, hypertrichosis, ichthyosis, clubbing, lower extremity edema, and hyperhidrosis. He also had numerous erythematous macules and papules on the trunk and proximal limbs that were compatible with multiple glomeruloid hemangiomas and cherry hemangiomas confirmed by biopsy. Serum immunoelectrophoresis/ immunofixation electrophoresis revealed an IgG lambda monoclonal gammopathy. Two bone marrow aspirations and biopsies were negative. A computed tomographic scan showed blastic and lytic lesions in the spine. Further laboratory examination of endocrine function revealed hypothyroidism, hypogonadism, and adrenal insufficiency. These findings led to the diagnosis of POEMS syndrome. He was treated by chemotherapy using melphalan and prednisone for three cycles but failed to respond. He then received cyclophosphamide and dexamethasone, again without clinical response. Later, the patient was seen in Dermatology for a sudden widespread eruption of violaceous plaques with irregular borders on his trunk and proximal extremities along with overall clinical deterioration. A skin biopsy obtained from a plaque on his left thigh showed microthrombi and widespread calcification of the small- to medium-sized blood vessels, typical of calciphylaxis (Figure 1). Laboratory examinations including complete blood count, renal and liver function, electrolytes including calcium, parathyroid hormone (PTH) levels, and autoimmune parameters were normal. The skin lesions quickly worsened into widespread necrotic and painful ulcers (Figure 2). He was transferred to a tertiary care center, and the calciphylaxis was treated with etidronate disodium and intravenous sodium thiosulfate. Bone lesions were treated by radiotherapy. A trial of bortezomib led to severe pain
Figure 1. Calcification of a small vessel in the panniculus (hematoxylineosin stain; original magnification 3 100).
2
Figure 2. Large retiform ulceration with eschar of the right suprapubic area surrounded by violaceous, indurated, tender, retiform plaques.
and violaceous discoloration of limbs. This medication was discontinued after three doses. Overall, the evolution was favorable despite widespread calciphylaxis with necrotic ulcers that were treated with split-thickness skin grafts and weekly intravenous sodium thiosulfate. Since his discharge from hospital and resolution of cutaneous ulcers, lenalidomide has been initiated, with significant results. The patient has residual distal neuropathic changes, but, otherwise, he completely recovered.
Discussion POEMS syndrome is a rare paraneoplastic disorder associated with an underlying plasma cell dyscrasia. To make a diagnosis, the major criteria of polyneuropathy and monoclonal plasmaproliferative disorder must be present. At least one of the minor criteria, excluding diabetes or thyroid abnormalities, must also be present: sclerotic bone lesions, Castleman disease, organomegaly, volume overload, endocrinopathy, skin changes, and papilledema.8 Other symptoms often associated with the syndrome include weight loss, fever, pulmonary function test abnormalities, fatigue, and diarrhea.9,10 Cutaneous manifestations, although generally nonspecific, have been shown to occur in 90% of patients with POEMS syndrome.10 Cutaneous findings include hyperpigmentation, hemangiomas, hypertrichosis, leukonychia, nail clubbing, sclerodermoid changes, and vascular skin changes such as Raynaud phenomenon, hyperemia/ erythema, flushing, rubor, acrocyanosis, and vasculitis, with patients reported as having a mean of three findings
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
POEMS Syndrome Complicated by Extensive Calciphylaxis
at diagnosis.10,11 The most common skin findings include hyperpigmentation and hemangiomas.10 The hyperpigmentation, which is seen in over 90% of patients,11 is usually generalized but can also have an acral or truncal distribution.10 Multiple hemangiomas, including cherry, lobular, and glomeruloid, are seen in up to 47% of patients,10 with the glomeruloid subtype considered to be a specific marker of the syndrome.12 Multiple theories have been proposed regarding the pathophysiology of skin changes seen in POEMS. Levels of vascular endothelial growth factor (VEGF) are elevated in patients with POEMS syndrome and seem to correlate with disease activity.12 It is plausible that the VEGF plays a role in the development of the cutaneous changes10; however, the relationship is not clear, and other possible etiologies, such as direct infiltration of malignant plasma cells, may also contribute to the observed skin changes.12 Cutaneous calciphylaxis is a severe microvascular occlusion disorder with a mortality rate of up to 89%.13 The disorder involves mural calcification, intimal proliferation, fibrosis, and thrombosis leading to painful lesions of noninflammatory retiform purpura and subsequent necrotic ulcerations.14 Numerous risk factors have been identified in the development of calciphylaxis, including renal failure, diabetes mellitus, hypoalbuminemia, obesity, liver disease, malignant neoplasm, chemotherapy, systemic inflammation, hepatic cirrhosis, protein C or S deficiency, rapid weight loss, infection, systemic glucocorticoid use, anticoagulation with warfarin, abnormalities in the calciumphosphate axis, and elevated serum aluminium.14,15 Hypercalcemia is a frequent finding in several neoplasms, especially in multiple myeloma; however, vascular calcification and calciphylaxis in association with neoplasia is a rare occurrence.15 Other than the paraneoplastic syndrome, our patient did not have any predisposing risk factors for this disorder. The pathogenesis underlying vascular calcification in calciphylaxis is complex and ultimately involves activation of the nuclear factor kB (NF-kB) pathway.15 The relative importance of the multiple factors leading to the calcium deposition is unclear, and most treatments thus far have focused on the calcium-phosphate-PTH axis, with successful results even in cases with no documented renal or parathyroid dysfunction.13 Although vascular calcification is the main element in calciphylaxis, the three components of the Virchow triad, including reduced blood flow, vascular endothelial injury, and hypercoagulability, are seemingly at the root of the disease, leading to the extensive ischemic necrosis observed.15
The mean survival after diagnosis of POEMS syndrome ranges from 8 to 13 years.11 However, up to 50% of patients with calciphylaxis die within 1 year of diagnosis, mainly due to sepsis.15 Proximal involvement of calciphylaxis, as in our case, has been associated with a poorer prognosis.3 We believe that our patient’s remarkable recovery is due to intense wound care and to the prompt initiation of treatment with a bisphosphonate and sodium thiosulfate, even in the context of a normal calciumphosphate axis. The impressive and sustained clinical improvement was also attributed to lenalidomide, which treated the underlying plasma cell dyscrasia. This case emphasizes that POEMS syndrome is a significant risk factor for calciphylaxis. Dermatologists should be aware of this possibility when following patients with the syndrome. Timely diagnosis is imperative with regard to prognosis. Our case clearly demonstrates that a favorable patient outcome is possible.
Acknowledgments Eric Gagne´, MD, kindly provided dermatopathology assistance. Financial disclosure of authors and reviewers: None reported.
References 1. Dispenzieri A, Buadi FK. A review of POEMS syndrome. Oncology (Williston Park) 2013;27:1242–50. 2. Stanciu M, Gagne´-Henley A, The´rien G. Unusual case of proximal calciphylaxis without renal failure. J Cutan Med Surg 2011;15:290–2. 3. Reiter N, El-Shabrawi L, Leinweber B, et al. Calcinosis cutis. J Am Acad Dermatol 2011;65:1–12, doi:10.1016/j.jaad.2010.08.038. 4. Hineno A, Kinoshita T, Kinoshita M, et al. Calciphylaxis as a catastrophic complication in a patient with POEMS syndrome. Case Rep Neurol 2009;1:47–53, doi:10.1159/000259906. 5. Lee FY, Chiu HC. POEMS syndrome with calciphylaxis: a case report. Acta Derm Venereol 2011;91:96–7, doi:10.2340/00015555-0986. 6. Yoshikawa M, Uhara H, Arakura F, et al. Calciphylaxis in POEMS syndrome: a case treated with etidronate. Acta Derm Venereol 2011;91:98–9. 7. De Roma I, Filotico R, Cea M, et al. Calciphylaxis in a patient with POEMS syndrome without renal failure and/or hyperparathyroidism. A case report. Ann Ital Med Int 2004;19:283–7. 8. Dispenzieri A, Kyle RA, Lacy MQ, et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101:2496–506, doi:10.1182/blood-2002-07-2299. 9. Miest RY, Comfere NI, Dispenzieri A, et al. Cutaneous manifestations in patients with POEMS syndrome. Int J Dermatol 2013;52: 1349–56, doi:10.1111/j.1365-4632.2012.05648.x. 10. Phillips JA, Dixon JE, Richardson JB, et al. Glomeruloid hemangioma leading to a diagnosis of POEMS syndrome. J Am Acad Dermatol 2006;55:149–52, doi:10.1016/j.jaad.2006.02.036.
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
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Bourgeault et al
11. Colaco SM, Miller T, Ruben BS, et al. IgM-lambda paraproteinemia with associated cutaneous lymphoplasmacytic infiltrate in a patient who meets diagnostic criteria for POEMS syndrome. J Am Acad Dermatol 2008;58:671–5, doi:10.1016/j.jaad.2007.07.021. 12. D’Souza A, Hayman SR, Buadi F, et al. The utility of plasma vascular endothelial growth factor levels in the diagnosis of POEMS syndrome. Blood 2011;118:4663–5, doi:10.1182/blood2011-06-362392.
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13. Kalajian AH, Malhotra PS, Callen JP, Parker LP. Calciphylaxis with normal renal and parathyroid function: not as rare as previously believed. Arch Dermatol 2009;145:451–8. 14. Weenig RH. Pathogenesis of calciphylaxis: Hans Selye to nuclear factor k-B. J Am Acad Dermatol 2008;58:458–71, doi:10.1016/ j.jaad.2007.12.006. 15. Alain J, Poulin YP, Cloutier RA, et al. Calciphylaxis: seven new cases. J Cutan Med Surg 2000;4:213–8.
Canadian Dermatology Association | Journal of Cutaneous Medicine and Surgery, 2014: pp 1–4
