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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Standardized incidence ratios &#40;SIR&#41; corresponding to 95&#37; confidence intervals shown according to cyanocobalamin level&#46; &#215; indicates 200&#8211;600&#8239;pmol&#47;L&#59; O&#44; 601&#8211;800&#8239;pmol&#47;L&#59; and &#9633;&#44; greater than 800&#8239;pmol&#47;L&#46; The vertical gray line represents a standardized incidence ratio of 1&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In their excellent study on erythroderma&#44; Cuellar-Barboza et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> analyze the various causes of this condition in adults&#46; The etiology is neoplastic or paraneoplastic in 1&#37; of cases&#44; and&#44; within this group&#44; erythroderma is most frequently associated with hematological malignancies and cutaneous T-cell lymphomas&#44; which account for 25&#37;&#8211;40&#37; of cases of erythroderma associated with cancer&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Of note&#44; the authors compile a series of laboratory findings and group them by frequency&#46; These have previously been reported in the literature and include elevated erythrocyte sedimentation rate&#44; leukocytosis&#44; eosinophilia&#44; anemia&#44; liver function&#44; and kidney function&#46; They highlight the importance of the eosinophil count in drug reaction with eosinophilia and systemic symptoms syndrome and call to mind the association between eosinophilia and malignant erythroderma&#46; Their approach stresses the usefulness of S&#233;zary cell count analysis in the diagnosis of S&#233;zary syndrome and mycosis fungoides&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Given the difficulty and importance of the diagnosis of paraneoplastic erythroderma&#44; we believe it would be interesting for the protocol put forward by the authors to include simple and accessible biomarkers that could assist in screening for tumors associated with erythroderma&#46; In this sense&#44; various studies have shown that increased levels of cyanocobalamin &#40;vitamin B<span class="elsevierStyleInf">12</span>&#41; are correlated with an increased risk of occult solid and hematologic malignancies&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Pathophysiology is based on the metabolism of cobalamin&#58; under normal conditions&#44; most cobalamin in blood &#40;80&#37;&#41; does not circulate freely and must bind to transport proteins&#44; namely&#44; haptocorrin<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;5</span></a> or type I transcobalamin&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5&#44;8</span></a> both of which can be synthesized by granulocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> In addition&#44; the levels of these transport proteins in blood are correlated with serum cobalamin levels&#44; thus explaining the high levels detected in blood dyscrasia&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Nevertheless&#44; high cobalamin levels have also been observed in some solid tumors &#40;e&#46;g&#46;&#44; pharynx&#44; esophagus&#44; liver&#44; stomach&#44; biliary tract&#44; pancreas&#44; lung&#44; colon-rectum&#44; prostate&#44; ovary&#44; cervix&#44; and bladder&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;7</span></a> possibly because the synthesis of type I transcobalamin could be increased by neoplastic cells themselves&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8</span></a> On the other hand&#44; since haptocorrin<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and type I transcobalamin<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> are metabolized in the liver&#44; primary tumors affecting the liver&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;8</span></a> metastases&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8</span></a> or other non&#8211;tumor-related causes<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6&#44;8</span></a> would make it possible to detect high serum cobalamin levels owing to the reduced clearance of the binding proteins&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Arendt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> conclude that&#44; while high cobalamin could be associated with smoking&#44; alcohol&#44; or liver disease&#44; levels above 800&#8239;pmol&#47;L are significantly associated with neoplasms&#44; especially hematologic malignancies&#44; such as non-Hodgkin lymphoma&#44; Hodgkin lymphoma&#44; multiple myeloma&#44; and leukemia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; We include the graph from Arendt et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> which shows the risk of diagnosing various types of tumor during the same year plasma cobalamin levels are determined&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">In this sense&#44; Chiche et al&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> demonstrate the statistically significant association between vitamin B<span class="elsevierStyleInf">12</span> concentrations greater than 1275&#8239;pg&#47;mL and hematologic malignancy&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Later studies<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6</span></a> reveal similar results and a poorer prognosis and higher mortality rates have been demonstrated for patients with cancer and elevated B<span class="elsevierStyleInf">12</span> levels than those with cancer and normal B<span class="elsevierStyleInf">12</span> levels&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; we believe that it would be interesting to include serum cobalamin levels in the erythroderma protocol of Cuellar-Barboza et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> since such a determination is simple&#44; inexpensive&#44; and accessible when screening for paraneoplastic erythroderma&#44; especially that associated with hematologic malignancy&#46;</p></span>"
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Vol. 112. Núm. 2.
Páginas 199-200 (febrero 2021)
Vol. 112. Núm. 2.
Páginas 199-200 (febrero 2021)
Letter to the Editor
Open Access
Role of Cyanocobalamin Levels in Managing Paraneoplastic Erythroderma: A Practical Approach
Papel de la cianocobalamina en el abordaje práctico de la eritrodermia paraneoplásica
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3779
A. Andamoyo-Castañeda, E. Gómez-Moyano
Autor para correspondencia
, D.J. Godoy Díaz, L. Martínez Pilar
Departamento de Dermatología, Hospital Regional Universitario de Málag, Málaga, Spain
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To the Editor:

In their excellent study on erythroderma, Cuellar-Barboza et al.1 analyze the various causes of this condition in adults. The etiology is neoplastic or paraneoplastic in 1% of cases, and, within this group, erythroderma is most frequently associated with hematological malignancies and cutaneous T-cell lymphomas, which account for 25%–40% of cases of erythroderma associated with cancer.

Of note, the authors compile a series of laboratory findings and group them by frequency. These have previously been reported in the literature and include elevated erythrocyte sedimentation rate, leukocytosis, eosinophilia, anemia, liver function, and kidney function. They highlight the importance of the eosinophil count in drug reaction with eosinophilia and systemic symptoms syndrome and call to mind the association between eosinophilia and malignant erythroderma. Their approach stresses the usefulness of Sézary cell count analysis in the diagnosis of Sézary syndrome and mycosis fungoides.

Given the difficulty and importance of the diagnosis of paraneoplastic erythroderma, we believe it would be interesting for the protocol put forward by the authors to include simple and accessible biomarkers that could assist in screening for tumors associated with erythroderma. In this sense, various studies have shown that increased levels of cyanocobalamin (vitamin B12) are correlated with an increased risk of occult solid and hematologic malignancies.1–8

Pathophysiology is based on the metabolism of cobalamin: under normal conditions, most cobalamin in blood (80%) does not circulate freely and must bind to transport proteins, namely, haptocorrin2–5 or type I transcobalamin,3,5,8 both of which can be synthesized by granulocytes.3,5 In addition, the levels of these transport proteins in blood are correlated with serum cobalamin levels, thus explaining the high levels detected in blood dyscrasia.2–8

Nevertheless, high cobalamin levels have also been observed in some solid tumors (e.g., pharynx, esophagus, liver, stomach, biliary tract, pancreas, lung, colon-rectum, prostate, ovary, cervix, and bladder),2–7 possibly because the synthesis of type I transcobalamin could be increased by neoplastic cells themselves.3,8 On the other hand, since haptocorrin4 and type I transcobalamin8 are metabolized in the liver, primary tumors affecting the liver,2,3,8 metastases,3,8 or other non–tumor-related causes3,6,8 would make it possible to detect high serum cobalamin levels owing to the reduced clearance of the binding proteins.

Arendt et al.2 conclude that, while high cobalamin could be associated with smoking, alcohol, or liver disease, levels above 800 pmol/L are significantly associated with neoplasms, especially hematologic malignancies, such as non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and leukemia (Fig. 1). We include the graph from Arendt et al.,2 which shows the risk of diagnosing various types of tumor during the same year plasma cobalamin levels are determined.

Figure 1.

Standardized incidence ratios (SIR) corresponding to 95% confidence intervals shown according to cyanocobalamin level. × indicates 200–600 pmol/L; O, 601–800 pmol/L; and □, greater than 800 pmol/L. The vertical gray line represents a standardized incidence ratio of 1.

(0.14MB).

In this sense, Chiche et al.3 demonstrate the statistically significant association between vitamin B12 concentrations greater than 1275 pg/mL and hematologic malignancy.

Later studies4,6 reveal similar results and a poorer prognosis and higher mortality rates have been demonstrated for patients with cancer and elevated B12 levels than those with cancer and normal B12 levels.4

In conclusion, we believe that it would be interesting to include serum cobalamin levels in the erythroderma protocol of Cuellar-Barboza et al.,1 since such a determination is simple, inexpensive, and accessible when screening for paraneoplastic erythroderma, especially that associated with hematologic malignancy.

References
[1]
A. Cuellar-Barboza, J. Ocampo-Candiani, M. Herz-Ruelas.
Eritrodermia en el adulto: un enfoque práctico para el diagnóstico y tratamiento.
Actas Dermo-sifiliogr., 109 (2018), pp. 777-790
[2]
J. Arendt, L. Pedersen, E. Nexo, H. Sørensen.
Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study.
J Natl Cancer Inst., 105 (2013), pp. 1799-1805
[3]
L. Chiche, R. Jean, F. Romain, S. Branger, K. Mazodier, G. Kaplanski, et al.
Implications cliniques de la découverte d’une hypervitaminémie B12 en médecine interne.
Rem Med Interne., 28 (2007), pp. 53-54
[4]
J. Arendt, D. Farkas, L. Pedersen, E. Nexo, H. Sorensen.
Elevated plasma vitamin B12 levels and cancer prognosis: a population-based cohort study.
Cancer Epidemiol., 40 (2016), pp. 158-165
[5]
J.F. Arendt, H.T. Sorensen, L.J. Horsfall, I. Petersen.
Elevated vitamin B12 levels and cancer risk in UK primary care: a THIN database cohort study.
Cancer Epidemiol Biomarkers Prev., 28 (2019), pp. 814-821
[6]
S. Brah, L. Chiche, J. Mancini, B. Meunier, J.B. Arlet.
Characteristics of patients admitted to internal medicine departments with high serum cobalamin levels: results from a prospective cohort study.
Eur J Intern Med., 25 (2014), pp. e57-e58
[7]
J. Ryg, M. Nybo, J. Hallas.
Cancer incidence in persons with elevated cobalamin levels.
Eur J Clin Invest., 43 (2013), pp. 557-561
[8]
M. Jammal, T. Deneuville, N. Mario, K. Tiev, C. Tolédano, L. Josselin-Mahr, et al.
High plasmatic concentration of vitamin B12: an indicator of hepatic diseases or tumors.
Rev Med Interne., 34 (2013), pp. 337-341

Please cite this article as: Andamoyo-Castañeda A, Gómez-Moyano E, Godoy Díaz DJ, Martínez Pilar L. Papel de la cianocobalamina en el abordaje práctico de la eritrodermia paraneoplásica. Actas Dermosifiliogr. 2021;112:199–200.

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