- Email: [email protected]
Cryofibrinogenemia. An uncommon cause of cold induced cutaneous lesions
372
Scientific letters / Med Clin (Barc). 2016;147(8):371–373
who have undergone gastrointestinal surgery. It is important to note that normal levels of 25-hydroxyvitamin D do not always prevent the development of hypertension, preeclampsia, gestational diabetes or low birth weight, as there are other pathophysiological mechanisms that also trigger these obstetric complications. In our country, vitamin D is not prescribed routinely to pregnant women; in cases where multivitamins are administered for pregnancy, the daily dose is 5 g (200 U) of cholecalciferol, which could prove insufficient in view of the results of this study.
4. Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013;346:f1169. 5. Pérez-López F, Pasupuleti V, Mezones-Holguin E, Benites-Zapata V, Thota P, Deshpande A, et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2015;103:1278–88.
María de la Calle a,∗ , Sara García b , Marta Duque c , José L. Bartha a a
References 1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S–6S. 2. Calatayud M, Jódar E, Sánchez R, Guadalix S, Hawkins F. Prevalencia de concentraciones deficientes e insuficientes de vitamina D en una población joven y sana. Endocrinol Nutr. 2009;56:164–9. 3. Pérez-López F, Fernández-Alonso AM, Ferrando-Marco P, González-Salmerón MD, Dionis-Sánchez EC, Fiol Ruiz G, et al. First trimester serum 25-hydroxyvitamin D status and factors related to lower levels in gravids living in the Spanish Mediterranean coast. Reprod Sci. 2011;18:730–6.
Cryofibrinogenemia. An uncommon cause of cold induced cutaneous lesions夽 Criofibrinogenemia. Una causa poco común de lesiones cutáneas inducidas por frío Dear Editor, Cryofibrinogenemia is a rare disease caused by deposition of cryofibrinogen in blood vessels. When this occurs at skin level, it causes various manifestations, such as cold intolerance, Raynaud’s phenomenon, purpura and livedo reticularis, among others.1 Next, we present a case of cryofibrinogenemia, a rare cause of livedoid lesions and purpura that typically worsen with cold. We report the case of a 54-year-old female, fishmonger by profession, without a medical or surgical history of interest. She had erythematous macules with a livedoid distribution in the lower extremities. Necrotic purpura was also observed in periungual regions, feet and Achilles tendon. Slightly palpable lesions were visible in the nasal tip. These began a few days earlier in the workplace. A blood lab test was requested, including blood count, coagulation, biochemistry, complement, proteins C and S, antithrombin iii, rheumatoid factor, ANA, ANCA, cryoglobulins, cryofibrinogen and cold agglutinin, antiphospholipid antibodies and serology tests for HBV and HCV, with results within normal limits. Histological examination showed a complete epidermal necrosis and numerous capillary PAS-positive thrombi in lumen, and polymorphonuclear leukocytes and nuclear debris in the surrounding area. All this was compatible with acute ischaemic damage, indicative of cryoglobulinemia or another “cryopathy”. The patient had a favourable progression with cold avoidance measures and a short course of oral prednisone 30 mg/day. Cryofibrinogen positivity was detected in a new lab test control, being diagnosed as essential cryofibrinogenemia. The patient is currently being monitored, remaining asymptomatic. Despite normal lab test results, haematology was
夽 Please cite this article as: Loidi Pascual L, Larumbe Irurzun A, Álvarez Gigli ML. Criofibrinogenemia. Una causa poco común de lesiones cutáneas inducidas por frío. Med Clin (Barc). 2016;147:372–373.
Servicio de Obstetricia y Ginecología, Hospital Universitario La Paz, Madrid, Spain b Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain c Servicio de Laboratorio, Hospital Universitario La Paz, Madrid, Spain ∗ Corresponding author. E-mail address: [email protected] (M. de la Calle).
2387-0206/ ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
consulted to assess the presence of a lymphoproliferative process that could have been developing cryofibrinogenemia as a secondary disease. After performing a complete lab test, this was ruled out. The tests included lymphocyte count, proteinogram, immunoglobulins and beta-2 microglobulin, chest radiography and abdominal ultrasound, which were all normal. In our case, the acute course of the lesions and the clear relationship with cold temperatures pointed towards an underlying systemic process, namely a cryoglobulinemia or another “cryopathy”. Despite the negativity in the tests requested, the suspected diagnosis of a clinical condition related to cryo-agglutination or cryogelling persisted, so the lab tests were repeated after some weeks. A positivity for cryofibrinogen could be demonstrated this time. Cryofibrinogen is a protein complex composed of fibrinogen, fibronectin, fibrin, and other components.2 Unlike cryoglobulin, it only precipitates in plasma, not in serum. Although the presence of cryofibrinogen in plasma can be asymptomatic, it is found in 12–51% of patients with suspected “cryopathies”. In a recent series of patients with this suspicion, half were positive for cryofibrinogen, from those, half had the essential type of the disease and another half a secondary form.3 The first and main cutaneous manifestations are usually in the form of intolerance to cold, Raynaud’s phenomenon, livedo reticularis and purpura. Necrosis, acral ulcers and gangrene can also occur, but less frequently. There may be general symptomatology and systemic arterial or venous thrombotic manifestations. Cryofibrinogenemia may be essential, but first we must rule out the association with other processes such as neoplasms, infections, autoimmune diseases or cryoglobulinemia. In the histopathological analysis, we can see cryofibrinogen deposits in the lumen of small and medium sized vessels, as eosinophilic refractile deposits, which become more evident with PAS staining. As for the differential diagnosis of cryoglobulinemia, both are two clinically and histologically indistinguishable conditions. The only difference is the type of protein that precipitates with the cold and that the cryofibrinogen is detected in plasma and the cryoglobulin in serum. The essential treatment is avoidance of cold temperatures. The clinical monitoring of these patients is essential because of the high risk of recurrence. Some series have shown the
Scientific letters / Med Clin (Barc). 2016;147(8):371–373
development of lymphomas after some years in patients diagnosed with essential cryofibrinogenemia.4
Leire Loidi Pascual ∗ , Amaia Larumbe Irurzun, Maria Laura Álvarez Gigli
References 1. Michaud M, Pourrat J. Cryofibrinogenemia. J Clin Rheumatol. 2013;19:142–8. 2. Herrero C, Guilabert A, Mascaró-Galy JM. Livedo reticularis de las piernas: metodología de diagnóstico y tratamiento. Actas Dermosifiliogr. 2008;99: 598–607. 3. Soyfoo MS, Goubella A, Cogan E, Wautrecht JC, Ocmant A, Stordeur P. Clinical significance of cryofibrinogenemia: possible pathophysiological link with Raynaud’s phenomenon. J Rheumatol. 2012;39:119–24. 4. Belizna C, Loufrani L, Subra JF, Godin M, Jolly P, Vitecocq O, et al. A 5-year prospective follow-up study in essential cryofibrinogenemia patients. Autoimmun Rev. 2011;10:559–62.
Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain ∗ Corresponding
author. E-mail address: [email protected] (L. Loidi Pascual). 2387-0206/ ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
373
Scientific letters / Med Clin (Barc). 2016;147(8):371–373
who have undergone gastrointestinal surgery. It is important to note that normal levels of 25-hydroxyvitamin D do not always prevent the development of hypertension, preeclampsia, gestational diabetes or low birth weight, as there are other pathophysiological mechanisms that also trigger these obstetric complications. In our country, vitamin D is not prescribed routinely to pregnant women; in cases where multivitamins are administered for pregnancy, the daily dose is 5 g (200 U) of cholecalciferol, which could prove insufficient in view of the results of this study.
4. Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013;346:f1169. 5. Pérez-López F, Pasupuleti V, Mezones-Holguin E, Benites-Zapata V, Thota P, Deshpande A, et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2015;103:1278–88.
María de la Calle a,∗ , Sara García b , Marta Duque c , José L. Bartha a a
References 1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S–6S. 2. Calatayud M, Jódar E, Sánchez R, Guadalix S, Hawkins F. Prevalencia de concentraciones deficientes e insuficientes de vitamina D en una población joven y sana. Endocrinol Nutr. 2009;56:164–9. 3. Pérez-López F, Fernández-Alonso AM, Ferrando-Marco P, González-Salmerón MD, Dionis-Sánchez EC, Fiol Ruiz G, et al. First trimester serum 25-hydroxyvitamin D status and factors related to lower levels in gravids living in the Spanish Mediterranean coast. Reprod Sci. 2011;18:730–6.
Cryofibrinogenemia. An uncommon cause of cold induced cutaneous lesions夽 Criofibrinogenemia. Una causa poco común de lesiones cutáneas inducidas por frío Dear Editor, Cryofibrinogenemia is a rare disease caused by deposition of cryofibrinogen in blood vessels. When this occurs at skin level, it causes various manifestations, such as cold intolerance, Raynaud’s phenomenon, purpura and livedo reticularis, among others.1 Next, we present a case of cryofibrinogenemia, a rare cause of livedoid lesions and purpura that typically worsen with cold. We report the case of a 54-year-old female, fishmonger by profession, without a medical or surgical history of interest. She had erythematous macules with a livedoid distribution in the lower extremities. Necrotic purpura was also observed in periungual regions, feet and Achilles tendon. Slightly palpable lesions were visible in the nasal tip. These began a few days earlier in the workplace. A blood lab test was requested, including blood count, coagulation, biochemistry, complement, proteins C and S, antithrombin iii, rheumatoid factor, ANA, ANCA, cryoglobulins, cryofibrinogen and cold agglutinin, antiphospholipid antibodies and serology tests for HBV and HCV, with results within normal limits. Histological examination showed a complete epidermal necrosis and numerous capillary PAS-positive thrombi in lumen, and polymorphonuclear leukocytes and nuclear debris in the surrounding area. All this was compatible with acute ischaemic damage, indicative of cryoglobulinemia or another “cryopathy”. The patient had a favourable progression with cold avoidance measures and a short course of oral prednisone 30 mg/day. Cryofibrinogen positivity was detected in a new lab test control, being diagnosed as essential cryofibrinogenemia. The patient is currently being monitored, remaining asymptomatic. Despite normal lab test results, haematology was
夽 Please cite this article as: Loidi Pascual L, Larumbe Irurzun A, Álvarez Gigli ML. Criofibrinogenemia. Una causa poco común de lesiones cutáneas inducidas por frío. Med Clin (Barc). 2016;147:372–373.
Servicio de Obstetricia y Ginecología, Hospital Universitario La Paz, Madrid, Spain b Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain c Servicio de Laboratorio, Hospital Universitario La Paz, Madrid, Spain ∗ Corresponding author. E-mail address: [email protected] (M. de la Calle).
2387-0206/ ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
consulted to assess the presence of a lymphoproliferative process that could have been developing cryofibrinogenemia as a secondary disease. After performing a complete lab test, this was ruled out. The tests included lymphocyte count, proteinogram, immunoglobulins and beta-2 microglobulin, chest radiography and abdominal ultrasound, which were all normal. In our case, the acute course of the lesions and the clear relationship with cold temperatures pointed towards an underlying systemic process, namely a cryoglobulinemia or another “cryopathy”. Despite the negativity in the tests requested, the suspected diagnosis of a clinical condition related to cryo-agglutination or cryogelling persisted, so the lab tests were repeated after some weeks. A positivity for cryofibrinogen could be demonstrated this time. Cryofibrinogen is a protein complex composed of fibrinogen, fibronectin, fibrin, and other components.2 Unlike cryoglobulin, it only precipitates in plasma, not in serum. Although the presence of cryofibrinogen in plasma can be asymptomatic, it is found in 12–51% of patients with suspected “cryopathies”. In a recent series of patients with this suspicion, half were positive for cryofibrinogen, from those, half had the essential type of the disease and another half a secondary form.3 The first and main cutaneous manifestations are usually in the form of intolerance to cold, Raynaud’s phenomenon, livedo reticularis and purpura. Necrosis, acral ulcers and gangrene can also occur, but less frequently. There may be general symptomatology and systemic arterial or venous thrombotic manifestations. Cryofibrinogenemia may be essential, but first we must rule out the association with other processes such as neoplasms, infections, autoimmune diseases or cryoglobulinemia. In the histopathological analysis, we can see cryofibrinogen deposits in the lumen of small and medium sized vessels, as eosinophilic refractile deposits, which become more evident with PAS staining. As for the differential diagnosis of cryoglobulinemia, both are two clinically and histologically indistinguishable conditions. The only difference is the type of protein that precipitates with the cold and that the cryofibrinogen is detected in plasma and the cryoglobulin in serum. The essential treatment is avoidance of cold temperatures. The clinical monitoring of these patients is essential because of the high risk of recurrence. Some series have shown the
Scientific letters / Med Clin (Barc). 2016;147(8):371–373
development of lymphomas after some years in patients diagnosed with essential cryofibrinogenemia.4
Leire Loidi Pascual ∗ , Amaia Larumbe Irurzun, Maria Laura Álvarez Gigli
References 1. Michaud M, Pourrat J. Cryofibrinogenemia. J Clin Rheumatol. 2013;19:142–8. 2. Herrero C, Guilabert A, Mascaró-Galy JM. Livedo reticularis de las piernas: metodología de diagnóstico y tratamiento. Actas Dermosifiliogr. 2008;99: 598–607. 3. Soyfoo MS, Goubella A, Cogan E, Wautrecht JC, Ocmant A, Stordeur P. Clinical significance of cryofibrinogenemia: possible pathophysiological link with Raynaud’s phenomenon. J Rheumatol. 2012;39:119–24. 4. Belizna C, Loufrani L, Subra JF, Godin M, Jolly P, Vitecocq O, et al. A 5-year prospective follow-up study in essential cryofibrinogenemia patients. Autoimmun Rev. 2011;10:559–62.
Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain ∗ Corresponding
author. E-mail address: [email protected] (L. Loidi Pascual). 2387-0206/ ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
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