Scurvy.

Dear Editor, Scurvy is a nutritional disorder which can develop after prolonged (>1-3 months) severe vitamin C deficiency. Vitamin C is a cofactor in several enzyme reactions involved in collagen synthesis. The defect in collagen causes blood vessel fragility, poor wound healing, mucocutaneous bleedings, hair abnormalities, bone pains, and joint contractures due to periosteal and intraarticular bleeding (1,2). Risk factors for scurvy development are undernutrition, low socioeconomic status, older age, male sex, alcoholism, tobacco smoking, and severe psychiatric illnesses (1-3). The required daily intake for vitamin C is ~60 mg, and this amount of vitamin C can be found in only one medium-sized orange. For this reason, the disease is rarely encountered in developed countries and is often underrecognized by healthcare personnel. Herein, we present an illustrative case of scurvy in order to raise the awareness of this disorder. A 61-year-old Caucasian man was admitted to hospital due to fatigue, hypotension (80/50 mmHg), severe normocytic anemia (hemoglobin 76 g/L), kidney failure (estimated glomerular filtration rate of 6 mL/min/1.73m2) and mild elevation in C-reactive protein (30.9 mg/L). Prior medical history included radical cystoprostatectomy with an ileal conduit performed eight years ago due to a bladder tumor and moderate chronic kidney disease with recurrent urinary tract infections. The patient was also an alcoholic and tobacco smoker, with a very low-income and a poor diet. He did not use any medications. Heteroanamnestically, the current clinical state had developed slowly over several weeks. At admission, the patient was afebrile, lethargic, malnourished, and immobile due to generalized weakness, bone pains, and hip and knee contractures. He had generalized edema, mostly related to kidney failure, as well as severe hypoalbuminemia (serum albumin 19 g/L). There were multiple ecchymoses (Figure 1, a) and perifollicular bleedings (Figure 1, b) in the skin. The teeth were defective, and the patient's facial hair had a "corkscrew" appearance (Figure 1, c). The platelet count was normal, as was the serum fibrinogen level and the prothrombin- and activated partial thromboplastin times. Vancomycin-resistant Enterococcus faecium and multi-drug-resistant Acinetobacter baumanii were isolated from the urine. Therefore, hemodialysis, linezolid, and colistin were started. However, the patient continued to be lethargic, immobile, and with prominent skin bleeding. Medical workup excluded the possibility of an underlying malignancy or an autoimmune disorder. Finally, scurvy was suspected and 500 mg daily of oral vitamin C was introduced into therapy. In the following two weeks, the general condition of the patient significantly improved and he was discharged from the hospital in good condition - mobile and with complete resolution of skin lesions (Figure 1, d and e). Three months later, the patient was still under maintenance hemodialysis and had mild anemia (hemoglobin 123 g/L). Interestingly, scurvy was the first disease in the history of medicine for which a randomized trial found a cure (4). The differential diagnosis of scurvy includes skin infections, hematologic disorders, collagen vascular disorders, and anticoagulant/antiplatelet side-effects (1). Pathognomonic skin findings which may help raise suspicion of scurvy are perifollicular bleedings and "corkscrew" hair. Notably, laboratory testing for vitamin C concentration is not necessary to confirm scurvy as it tends to reflect recent dietary intake of vitamin C (2). Nevertheless, it may be useful to identify less typical cases (2). In our case, rapid clinical improvement with the resolution of skin lesions and joint contractures after the introduction of vitamin C confirmed the clinical diagnosis of scurvy. Additionally, vitamin C deficiency could be, at least partly (besides kidney failure and acute infection), responsible for severe anemia at disease presentation (5). This case serves to remind clinicians not to forget scurvy when treating patients at risk for vitamin C deficiency who present with fatigue, anemia, bone pains, and unexplained mucocutaneous bleedings. In suspected cases, vitamin C should be administered without hesitation.

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress.

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L, p < 0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs. 24 ± 14 µmol/L, p = 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (p < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (p = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery.

Escorbuto. Comunicación de un caso y revisión de la literatura / SCURVY - CASE REPORT AND LITERATURE REVIEW

El escorbuto es una enfermedad ocasionada por el déficit de vitamina C. La vitamina C, también llamada ácido ascórbico, actúa como cofactor de la propil-lisil hidroxilasa, enzima que interviene en la biosíntesis de colágeno; por ello es de vital importancia en la integridad estructural de piel, mucosas, anexos, vasos sanguíneos, huesos y dientes. Las manifestaciones clínicas incluyen síntomas constitucionales severos como debilidad y fatiga. Los hallazgos cutáneos iniciales son pápulas hiperqueratósicas foliculares y púrpura palpable perifolicular. Con el tiempo aparecen áreas extensas de equimosis, edema en miembros inferiores, hemorragias en astillas en uñas y alopecia difusa. Por lo general se describe esta enfermedad como asociada a tiempos pasados y extremadamente infrecuente en países desarrollados. Sin embargo, actualmente se ha detectado un aumento en el número de casos, asociados con malnutrición severa. Desórdenes psiquiátricos como la anorexia nerviosa, alcoholismo y deficiencias nutricionales por dietas excesivas y mal balanceadas o escasez de recursos económicos constituyen los principales factores de riesgo hoy en día. El tratamiento consiste en la corrección del déficit mediante la mediante suplementación con vitamina C vía oral. Presentamos una mujer de 24 años con escorbuto asociado a anorexia nerviosa y a dieta pobre en vegetales y fruta.

Scurvy is a disease caused by a deficit of vitamin C. Vitamin C, also called ascorbic acid, acts as a cofactor for propyl-lysyl hydroxylase, an enzyme that is involved in collagen biosynthesis, vitally important in the structural integrity of skin, mucous membranes, annexes, blood vessels, bones and teeth. Clinical manifestations include severe constitutional symptoms such as weakness and fatigue. The initial cutaneous findings are follicular hyperkeratotic papules and perifollicular palpable purpura. Over time, large areas of ecchymosis, edema of the lower limbs, splinter hemorrhages in nails and diffuse alopecia appear. Usually this disease is described as associated with past times and extremely uncommon in developed countries. However, the number of cases have been increasing, especially those associated with severe malnutrition. Psychiatric disorders such as anorexia nervosa, alcoholism and nutritional deficiencies due to excessive and poorly balanced diets or shortage of economic resources are the main risk factors nowadays. Correcting the deficit with oral vitamin C supplementation is the treatment of the disease. We present a 24-year-old woman with scurvy associated with anorexia nervosa and a diet low in vegetables and fruit.

Vitamin C for the critically ill: Is the evidence strong enough?

Vitamin C exhibits interesting properties in the context of critical illness, with benefits described in neurologic, cardiovascular, renal, and hematologic systems, both in in vitro and in animal models. Through direct effects on bacterial replication, immunomodulation, and antioxidant reserve of the organism, vitamin C directly affects the pathophysiological process of sepsis, trauma, burn, and systemic inflammation. Even if several observational trials have linked vitamin C deficiency to worse outcomes, the evidence is not such as to provide us with a distinction between causality effects or simple epiphenomenon, and the current focus is on interventional trials. Pharmacokinetic data suggest that a minimal supplementation of 3 g/d intravenously is required to restore normal serum values in critically ill patients with known deficiency. According to these data, only five trials, including a retrospective analysis, studied pharmacologic dose: three as an antioxidant cocktail and two as monotherapy. The largest trial, conducted in 2002, reported reduced incidence of multiorgan failure and duration of mechanical ventilation. Recently a retrospective analysis reported impressive results after administration of vitamin C, thiamine, and hydrocortisone. The two most recent trials reported improved clinical outcomes, including improved mortality, but contained significant methodological limitations. A recent systematic review did not find clinical benefits with the most-studied low-dose oral supplementation, potentially because of suboptimal or insufficient repletion. Current guidelines do not support the administration of high-dose vitamin C in critically ill patients. Future larger trials are required to support any therapy, but the low cost and safety profile can justify supplementation in the meantime. Metabolomics study will further help understand biological effect.

Lessons in early identification and treatment from a case of disabling vitamin C deficiency in a child with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder is a heterogenous neurodevelopmental condition accompanied by a variety of associated features. Case reports suggest one such associated feature, food selectivity, increases risk for nutritional deficiencies; however, little attention has been given to prevent and treat nutritional deficiencies in youth with autism spectrum disorder. METHOD: Single case report. RESULTS: This single case report presents a child with autism spectrum disorder and food selectivity difficulties that resulted in severe vitamin C deficiency. Although eventually corrected, the nutritional deficiency was debilitating, required invasive interventions, and resulted in significant social/emotional and economic costs. CONCLUSIONS: We review the course of treatment and highlight strategies to prevent and more effectively treat nutritional deficiencies in youth with autism spectrum disorder.

Attenuation of sepsis-induced organ injury in mice by vitamin C.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is the principal cause of death in patients with sepsis. Recent work supports the notion that parenteral vitamin C (VitC) is protective in sepsis through pleiotropic mechanisms. Whether suboptimal levels of circulating VitC increase susceptibility to sepsis-induced MODS is unknown. MATERIALS AND METHODS: Unlike mice, humans lack the ability to synthesize VitC because of loss of L-gulono-γ-lactone oxidase (Gulo), the final enzyme in the biosynthesis of VitC. To examine whether physiological levels of VitC are required for defense against a catastrophic infection, we induced sepsis in VitC sufficient and VitC deficient Gulo(-/-) mice by intraperitoneal infusion of a fecal stem solution (FIP). Some VitC deficient Gulo(-/-) mice received a parenteral infusion of ascorbic acid (AscA, 200 mg/kg) 30 minutes after induction of FIP. We used molecular, histological, and biochemical analyses to assess for MODS as well as abnormalities in the coagulation system and circulating blood cells. RESULTS: FIP produced injury to lungs, kidneys and liver (MODS) in VitC deficient Gulo(-/-) mice. MODS was not evident in FIP-exposed VitC sufficient Gulo(-/-) mice and attenuated in VitC deficient Gulo(-/-) mice infused with AscA. Septic VitC deficient Gulo(-/-) mice developed significant abnormalities in the coagulation system and circulating blood cells. These were attenuated by VitC sufficiency/infusion in septic Gulo(-/-) mice. CONCLUSIONS: VitC deficient Gulo(-/-) mice were more susceptible to sepsis-induced MODS. VitC sufficiency or parenteral infusion of VitC, following induction of sepsis, normalized physiological functions that attenuated the development of MODS in sepsis.

[Vitamin C]. / Vitamine C.

Vitamin C is a water soluble vitamin which is mainly fresh fruits and vegetables foodborne. Vitamin C deficiency is most often due to a lack of daily amount. Scurvy is characterized by the occurrence of fatigue, myalgia, arthralgia, purpura, bleeding disorders, and later by dental manifestations. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion is confirmed by the decrease in ascorbic acid level (< 2 mg/L). It must be interpreted in light of the acute phase reactants. The treatment is the administration of 1 g of vitamin C per day for 15 days. Vitamin C depletion (ascorbic acid: 2 to 5 mg/L) could induce long-term complications. The recommended dietary allowance of vitamin C protect from these risks.

A rare case of scurvy in an otherwise healthy child: diagnosis through oral signs.

The purpose of this paper was to report the case of a 2-year-old Caucasian female who was referred with a presumed diagnosis of pediatric rheumatoid arthritis. The patient presented widespread gingival swelling with bleeding, sharp pain, and halitosis. The patient also presented pain and swelling of the right knee joint, and psychomotor restlessness associated with muscular frailty. Little compliance on the part of both the patient and parents was also noted. Oral manifestations, together with an accurate medical history, led to the diagnosis of infantile scurvy, caused by an inadequate dietary supply of vitamin C. Administering 250 mg of ascorbic acid orally twice a day led to the remission of gingival swelling and of the other symptoms. The parents were advised to feed the child appropriate foods. Nutritional problems are traditionally linked to an insufficient availability of food, but can also be associated with child- or family-related psychological problems.

Nutritional deficiencies during normal growth.

Nutritional deficiencies have always been a major consideration in pediatrics. Although the classic forms of many of the well-documented nutritional deficiencies are memorized during training as a physician, nutritional deficiencies that can occur in otherwise asymptomatic normally growing children are often overlooked. The two most common deficiencies seen in children who are growing normally are iron and vitamin D deficiencies. These deficiencies are surprisingly common and can have a significant impact on the overall health of a child. This article reviews these nutritional deficiencies and other less commonly seen deficiencies in children who are otherwise growing normally.

Vitamina C / Vitamin C

La vitamina C o ácido ascórbico es una vitamina hidrosoluble derivada del metabolismo de la glucosa. Actúa como agente reductor y es necesaria para la síntesis de las fibras de colágeno a través del proceso de hidroxilación de la prolina y de la lisina. También protege al organismo del daño causado por los radicales libres. Los humanos no podemos sintetizar ácido ascórbico al carecer de una enzima denominada gulonolactonaoxidasa. Las concentraciones en plasma y leucocitos reflejan los niveles de la dieta y los depósitos corporales respectivamente de dicha vitamina. Entre los alimentos con niveles altos de vitamina C figuran tomates, patatas y cítricos como las limas, naranjas y limones. La recomendación actual de ingesta diaria de vitamina C es de 90 mg/día para hombres y de 75 mg/día para mujeres. Los pacientes con enfermedades crónicas como el cáncer o la diabetes o los fumadores necesitan dosis mayores en su dieta habitual. El déficit de ácido ascórbico da lugar a la aparición del escorbuto. Esta enfermedad se ve raramente en países desarrollados. Los síntomas se desarrollan con niveles plasmáticos inferiores a 0,15 mg/dl. El escorbuto se caracteriza por la presencia de debilidad, dolor articular o lesiones cutáneas en forma de petequias, sangrado de encías, facilidad para desarrollar hematomas o retraso en la curación de las heridas. Las manifestaciones cutáneas más características son las pápulas purpúricas hiperqueratósicas perifoliculares y la presencia de pelos ensortijados

Vitamin C or ascorbic acid is a hydrosoluble vitamin derived from glucose metabolism. It acts as a reductor agent required for synthesis of collagen fibers through hydroxylation of proline and lysine. It also protects the body against damage caused by the free radicals. Humans cannot synthesize ascorbic acid as they lack an enzyme called gulonolactone oxidase. Concentrations in plasma and leukocytes reflect the levels of the diet and body deposits respectively of this vitamin. Among foods with high vitamin C levels are tomatoes, potatoes, and citric fruits such as limes, oranges and lemons. The current recommendation of daily intake of vitamin C is 90 mg/d for men and 75 mg/d for women. Patients with chronic diseases such as cancer or diabetes or those who smoke need higher doses in their usual diet. Ascorbic acid deficiency gives rise to the appearance of scurvy. This disease is rarely seen in developed countries. The symptoms develop with plasma levels below 0.15 mg/dL. Scurvy is characterized by the presence of weakness, joint pain or skin lesions in form of petechias, gum bleeding, ease of developing bruises or delay in wound healing. The most characteristic skin manifestations are purpuric perifollicular hyperkeratotic papules and the presence of kinky hair

[Vitamin C deficiency]. / Carences en vitamine C.

BACKGROUND: Hypovitaminosis C is frequent in populations at risk (men who live alone, old people, homelessness, patients with psychiatric diseases, foodfaddists,...) and is underestimated in the general population. STRONG POINTS: Scurvy occurs after 3 months without consumption of ascorbic acid, and is due to lack of consumption fresh fruits and vegetables. Clinical manifestations are weakness, myalgia and arthralgia, vascular purpura and hemorrhagic syndrome, and later the stomatologic manifestations: gingivorragia and loss of teeth. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion must be confirmed by a low level of ascorbic acid (<2.5 mg/l), but this value needs to be interpretated according to the presence of an acute phase response. Leucocyte ascorbic acid level reflects total body store and is more reliable, but not available in practice. Treatment consists in administration of 1 g vitamin C per day during 15 days. PERSPECTIVES: Vitamin C depletion (serum ascorbic acid level between 2 and 5 mg/l) may occur long-term complications such as increase cardiovascular and neoplasic risks or cataract. The new recommended dietary allowance of vitamin C (110 mg per day for an adult) takes into account of these risks.

Vitamin nutrition in older adults.

Proper vitamin nutrition is essential for all people but especially for elderly persons, because they are at higher risk for deficiency than younger adults. A review of the clinical effects of vitamin deficiency shows how easily deficiency can masquerade as other morbidities, such as skin, neurologic, and gait abnormalities. Given the numerous readily available forms and sources of supplementation, their low cost, and their rather limited potential for harm, the goal of good vitamin nutrition for the elderly is easily attainable. To be successful in this goal, physicians must look for patients at risk and for those with features of frank vitamin deficiency. Laboratory testing is most helpful with respect to vitamin B12 and folate deficiency. Given the great value of clinical assessment, the low cost of vitamins, and the higher cost of laboratory testing, the authors do not recommend testing before instituting multivitamin use or extra supplementation with individual vitamins unless the diagnosis of deficiency is in question or the use of supplementation would put the patient at risk. The authors' general recommendations are * one multivitamin daily * extra vitamin E for patients with cardiovascular risk factors or Alzheimer's dementia * extra vitamin D for patients with known osteoporosis, osteoporosis risk factors, or strong risk factors for vitamin D deficiency * extra folate for patients with cardiovascular risk factors (especially smokers) and alcoholics * extra thiamine for alcoholics.

Functional assessment of proliferating hepatocytes stimulated by hepatic stimulatory substance in ascorbic acid biosynthetic enzyme-deficient rats.

The functional ability of hepatic stimulatory substance (HSS)-stimulated proliferating hepatocytes was investigated by intrasplenic and/or intraportal transplantation in ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats that die of osteogenic disorders unless there is AsA supplementation. HSS was extracted from regenerating porcine livers. Hepatocytes isolated from the livers of congeneic ODS-+/+ rats that are capable of synthesizing AsA were transplanted into the spleen (Sp-HTx) and/or the portal vein (Pv-HTx) of ODS-od/od rats. The recipients were divided into eight groups as follows: HSS-untreated groups [group Ia, sham-operated, HTx(-); group IIa, Sp-HTx; group IIIa, Pv-HTx; and group IVa, Sp- and Pv-HTx], HSS-treated groups [group Ib, HSS only; group IIb, Sp-HTx + HSS; group IIIb, Pv-HTx + HSS; and group IVb, Sp- and Pv-HTx + HSS]. The recipients were given a diet and water containing AsA for 6 weeks after HTx, and AsA supplementation was then halted. The average bromodeoxyuridine (BrdU) labeling index (LI) and hepatocyte-occupied ratio in the spleen (H/S ratio) of HSS-treated rats were significantly higher than those of HSS-untreated rats. All the rats in HSS-untreated groups and group Ib died by 8 weeks after the cessation of AsA. In HSS-treated groups IIb, IIIb, and IVb, the survival rates were 60%, 50%, and 80%, respectively, at 16 weeks after HTx. The average serum AsA level of the surviving rats in groups IIb, IIIb, and IVb was significantly higher than that in HSS-untreated groups. These results indicate that HSS treatment induced rapid proliferation of transplanted hepatocytes in the spleen and the portal vein, and that these proliferating hepatocytes synthesized AsA and improved the survival rate of ODS-od/ od rats.

Multilocational hepatocyte transplantation for treatment of congenital ascorbic acid deficiency rats.

We attempted multilocational hepatocyte transplantation (HCTx) including hepatocyte-bearing polyurethane foam (PUF) to treat congenitally ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats. Hepatocytes isolated from the liver of congeneic rats were transplanted into the portal vein (Pv), spleen (Sp), omentum (Om), and mesentery (Ms). Hepatocyte-bearing PUF was transplanted into the Om and Ms. Experimental groups were divided into four groups (group I; Pv + Sp, group II; Pv + Sp + Om + Ms, group III; Pv + Sp + hepatocyte-bearing PUF, group IV; control). The average serum AsA level of the surviving rats in group II and III was significantly higher than that in group I 3 mo after HCTx. Histological examination showed small foci of surviving hepatocytes in the Om and Ms tissues and in the connective tissue in the PUF. ODS-od/od rats survived for a long time by multilocational HCTx.