Vitamin deficiencies in children: Lessons from clinical and neuroimaging findings.

BACKGROUND AND AIMS: Water-soluble vitamins play an essential coenzyme role in the nervous system. Acquired vitamin deficiencies are easily treatable, however, without treatment, they can lead to irreversible complications. This study aimed to provide clinical, laboratory parameters and neuroimaging data on vitamin deficiencies in an attempt to facilitate early diagnosis and prompt supplementation. METHODS: From July 1998 to July 2023, patients at Necker-Enfants-Malades Hospital presenting with acute neurological symptoms attributed to acquired vitamin deficiency were included. Clinical data were extracted from Dr Warehouse database. Neuroimaging, biochemical and electrophysiological data were reviewed. RESULTS: Patients with vitamin B1 deficiency exhibited abnormal eye movements (n = 4/4), fluctuations in consciousness (n = 3/4), and ataxia (n = 3/4). Brain MRI showed alterations of fourth ventricle region (n = 4/4), periaqueductal region (n = 4/4), tectum (n = 3/4), and median thalami (n = 3/4). Patients with vitamin B2 deficiency presented with early onset hypotonia (n = 3/4), hyperlactatemia (n = 4/4), and hyperammonemia (n = 4/4). Plasma acylcarnitines revealed a multiple acyl-coA dehydrogenase deficiency-like profile (n = 4/4). In vitamin B12 deficiency, young children presented with developmental delay (n = 7/7) and older children with proprioceptive ataxia (n = 3/3). Brain MRI revealed atrophy (n = 7/7) and spinal MRI hyperintensity in posterior cervical columns (n = 3/3). Metabolic findings showed elevated methylmalonic acid (n = 6/7) and hyperhomocysteinemia (n = 6/7). Patients with vitamin C deficiency exhibited gait disturbances and muscle weakness (n = 2/2). CONCLUSIONS: Acquired vitamin deficiencies may display reversible clinical symptoms mimicking inherited metabolic disorders. Some situations raise suspicion for diagnosis: concordant clinical presentation, suggestive neuroimaging findings, and/or biochemical evidence. Any acute neurological condition should be treated without waiting for definitive biochemical confirmation.

An Unusual Etiology of Severe Right Heart Failure Deserving of Wider Recognition.

A previously healthy 31-year-old man presented with worsening shortness of breath and a petechial rash. Echocardiography showed severe right-sided heart failure with midsystolic notching of the antegrade right ventricular outflow Doppler envelope suggesting pulmonary hypertension. An extensive work-up revealed scurvy, with a dramatic resolution of symptoms shortly after vitamin C supplementation.

Severe Acute Malnutrition Presenting With Scurvy: A Case Report.

Scurvy is a disease caused by a lack of vitamin C. It is a nutritional deficiency that is associated with multiple severe conditions. Although developed countries report these cases rarely now due to advancements in food and nutritional supplements, they are still prevalent in developing countries, albeit rare, because of poor nutritional status. Due to the lower prevalence of scurvy, diagnosis is delayed in the majority of cases and sometimes missed completely, which results in serious complications and unnecessary workups. Here, we present a rare case of a four-year-old female child with severe acute malnutrition (SAM) presenting with scurvy. The initial clinical signs showed SAM. X-ray and MRI of the left femur and knee were done to further evaluate the orthopedic parameters. Clinical presentation and radiographic imaging confirmed all the signs of scurvy. The patient was started on the Formula 75 (F-75) diet to address the severe malnutrition, and steady weight gain was observed.

A Case of Scurvy Associated With Intracerebral Hemorrhage in a Patient With Alcohol Use Disorder.

Vitamin C deficiency, also known as scurvy, causes abnormalities in connective tissues and varied symptoms. We describe a patient with putaminal hemorrhage, a very rare presentation of scurvy. A 39-year-old man presented with weakness in the left arm and left leg. Right putaminal hemorrhage was initially diagnosed, and he underwent evacuation of the intracerebral hemorrhage. Scurvy was suspected when repeated physical examinations revealed a bleeding tendency and multiple untreated dental caries, missing teeth, and gingivitis. A diagnosis of scurvy was further supported by the patient's history of smoking, alcohol use disorder, poor diet, and low plasma vitamin C concentration. After receiving oral nutritional supplementation including vitamin C, the bleeding tendency quickly improved. This case highlights the importance of including scurvy in a differential diagnosis for patients with bleeding tendencies, especially those with a poor diet or unknown dietary history. Empirical administration of vitamin C is a reasonable treatment.

Prevalence, risk factors, and clinical outcomes of vitamin C deficiency in adult hospitalized patients in high-income countries: a scoping review.

BACKGROUND: Assessment for vitamin C deficiency (VCD) is rarely undertaken in an acute hospital setting in high-income countries. However, with growing interest in VCD in community settings, there is emerging evidence investigating the prevalence and impact of VCD during hospitalization. OBJECTIVES: In this scoping review, the prevalence of VCD in adult hospitalized patients is explored, patient characteristics are described, and risk factors and clinical outcomes associated with VCD are identified. METHODS: A systematic scoping review was conducted in accordance with the PRISMA-ScR framework. The Ovid MEDLINE, Ovid Embase, Scopus, CINAHL Plus, Allied and Complementary Medicine Database, and the Cochrane Library databases were searched for interventional, comparative, and case-series studies that met eligibility criteria, including adult hospital inpatients in high-income countries, as defined by the Organization for Economic Co-operation and Development, that reported VCD prevalence using World Health Organization reference standards. These standards define VCD deficiency as plasma or serum vitamin C level <11.4 µmol/L, wholeblood level <17 µmol/L, or leukocytes <57 nmol/108 cells. RESULTS: Twenty-three articles were included, representing 22 studies. The cumulative prevalence of VCD was 27.7% (n = 2494; 95% confidence interval [CI], 21.3-34.0). High prevalence of VCD was observed in patients with severe acute illness and poor nutritional status. Scurvy was present in 48% to 62% of patients with VCD assessed in 2 studies (n = 71). Being retired (P = 0.015) and using excessive amounts of alcohol and tobacco (P = 0.0003) were independent risk factors for VCD (n = 184). Age was not conclusively associated with VCD (n = 631). Two studies examined nutrition associations (n = 309); results were inconsistent. Clinical outcomes for VCD included increased risk of frailty (adjusted odds ratio, 4.3; 95%CI, 1.33-13.86; P = 0.015) and cognitive impairment (adjusted odds ratio, 2.93; 95%CI, 1.05-8.19, P = 0.031) (n = 160). CONCLUSIONS: VCD is a nutritional challenge facing the healthcare systems of high-income countries. Research focused on early identification and treatment of patients with VCD is warranted. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/AJGHX ).

Ascorbic acid deficiency amongst spondylodiscitis patients.

BACKGROUND: Spondylodiscitis can be a disabling and life-threatening infection. Ascorbic Acid is crucial for neutrophil function and collagen formation. Its association and clinical relevance in spondylodiscitis has not been previously examined. AIMS: To determine the prevalence, characteristics, and clinical outcomes of spondylodiscitis patients with Ascorbic Acid deficiency. METHODS: Sixty-eight consecutive patients admitted with spondylodiscitis, between December 2021 and August 2023 were included. Clinical characteristics, Ascorbic Acid levels and clinical outcomes were evaluated. RESULTS: Thirty-seven patients had Ascorbic Acid levels taken during admission. The median initial Ascorbic Acid level was 15 µmol/L with an IQR 6.5-27 µmol/L. Depletion defined as <28 µmol/L was present in 78% of patients. Deficiency defined as ≤11 µmol/L was present in and 46% of patients. Patients with depletion were more likely to require Intensive Care Admission (absolute risk increase = 24.1%; 2.6%-45.7%). Fifteen patients had repeat serum levels taken during admission with median increase of 17 µmol/L and an IQR 0-26 µmol/L. Patients that received supplementation had a significantly greater increase in Ascorbic Acid levels compared with those that did not receive supplementation (P = 0.002). CONCLUSION: Ascorbic acid deficiency is highly prevalent amongst spondylodiscitis patients. Depletion was associated with worse outcomes. Replacement significantly increased serum levels in comparison to standard hospital diet. The clinical significance of replacement remains to be evaluated.

Lessons learned from "the great mimicker disease": A retrospective study of 18 patients with scurvy.

Purpose: Scurvy is an uncommon medical condition that affects children and is caused by an inadequate intake of vitamin C. This study presents the characteristics of patients with scurvy to raise awareness of the diagnostic process in developing countries where laboratory testing for vitamin C levels is often not available. Methods: A retrospective study was performed from period of 2018 to 2023. Data extraction includes patient age, sex, body mass index, constitutional symptoms, musculoskeletal, mucosal, cutaneous symptoms, other accompanying disorders, anemia, erythrocyte sedimentation rate, C-reactive protein, radiographic examination, vitamin C dose, and duration of treatment. Descriptive statistical analysis was performed in this study. Results: Eighteen cases (17 males, 1 female) of scurvy were referred to our institution. Thirteen of 18 patients were misdiagnosed before referral. The median age at presentation was 4.5 (range, 2-11) years. The average body mass index was 13.93 ± 0.63 kg/m2. Half of patients had healthy weight. All patients presented with lower limb pain and 17 of 18 with refusal to walk. The median onset of diagnosis was 11 (range 4-48) weeks. White line of Frankel was described in all patients. Seven had anemia and 6 of 18 had increase in erythrocyte sedimentation rate and/or C-reactive protein levels. Only one patient had ascorbic acid levels evaluation before treatment since it was not readily available in our country. Treatment length varied from 2 weeks to 6 months. Conclusion: The diagnosis of scurvy is frequently delayed due to its extreme rarity in modern society and its ability to mimic numerous other conditions. In children presenting with limb pain and/or reluctance to walk and pathognomonic radiological findings, physicians must prioritize scurvy as a differential diagnosis. In scurvy, vitamin C supplementation is curative.

A Rare Presentation of Scurvy in a Well-Nourished Patient.

Vitamin C deficiency, otherwise known as scurvy, is a rare diagnosis among populations with adequate nutritional resources. We present a 37-year-old female patient with bilateral lower extremity edema, episodic anasarca, petechiae, and easy bruising who was diagnosed with scurvy. Given the clinical presentation, a broad differential was investigated with no findings suggestive of hematologic or cardiovascular pathology. Initial laboratory studies were unremarkable. Progression of cutaneous symptoms and subsequent laboratory findings demonstrating low vitamin C levels supported a diagnosis of scurvy. Classical symptoms of scurvy include mucocutaneous petechiae, poor wound healing, ecchymosis, hyperkeratosis, corkscrew hair, gingival swelling, and bleeding gums. Following standard enteral supplementation of vitamin C, repeat vitamin C levels failed to adequately respond with the patient remaining to be symptomatic. Given a lack of insufficient nutritional intake or known systemic illness, gastrointestinal malabsorptive etiology was suspected. Though rare in the United States, scurvy should be considered in patients with manifestations of a bleeding disorder. A gastrointestinal workup may be indicated if other nutritional deficiencies are identified, or a source of inadequate intake cannot be established.

Scurvy: A treatable forgotten fatal differential diagnosis and potential etiology of leukemia and aplastic anemia in pediatric population.

Scurvy is a rare nutritional deficiency disease which is less likely to be suspected and it mostly lead to delayed diagnosis. It can present with features which can mislead clinicians to misdiagnose the condition as leukemia or aplastic anemia. This can subject patients to the wrong management which leads to poor outcome and increased preventable morbidity and mortality. Vitamin C deficiency is still prevalent among pediatric population even in the modern days and should no longer be considered as historical condition. Chromosomal fragility has been greatly accounted for the development of leukemia and aplastic anemia secondary to various triggers. The role of vitamin C toward DNA stability, prevention, and control of mutations have been documented. Vitamin C plays a vital role in hematopoiesis by controlling regulation and prevent dysfunction of hematopoietic stem cells. Scurvy deficiency has been a silent growing clinical problem which needs a high index of suspicion for a clinician to pick it. It should be considered as one among potential differential diagnosis of leukemia and aplastic anemia especially in the pediatric population. History of any dietary restriction should be obtained and addressed properly. Serum vitamin C should be among the essential laboratory workout in diagnosis of both leukemia and aplastic anemia. All patients suspected to have such conditions should be screened and supplemented for vitamin C deficiency irrespective of positive confirmatory test results of leukemia or aplastic anemia since the probability of co-occurrence is likely also. Moreover, studies should be conducted to explore the clinical link, if any, between vitamin C deficiency or insufficiency and development of leukemia and aplastic anemia among the pediatric population given its physiological and genomic role in hematopoiesis. Furthermore, the potential pharmacological therapeutic use of vitamin C in treatment of leukemia and aplastic anemia should be determined clinically.

Haemorrhagic Pericardial Effusion as the Presenting Symptom of Scurvy.

Introduction: Vitamin C deficiency (or scurvy) usually takes weeks to become apparent as cutaneous signs and impaired wound healing. Haemorrhagic pericarditis remains a rare complication of scurvy, which has never been reported as an isolated condition. We report the case of a haemorrhagic pericarditis revealing a vitamin C deficiency in a 56-year-old patient. Case description: A 56-year-old woman presented with a 2-week history of worsening chest pain and dyspnoea, with no significant medical history. Upon admission, the patient exhibited tachycardia, tachypnoea, low blood pressure, elevated jugular venous pressure, muffled heart sounds and multiple petechiae on her lower limbs. An ultrasound revealed a large pericardial effusion, and an emergency pericardiocentesis was performed, which yielded haemorrhagic fluid without atypical cells. An initial workup including haemoculture, PT and PTT, tuberculosis workup, autoantibodies, tumour markers and infectious disease was negative. A whole-body CT scan showed no evidence of tuberculosis or lymphoma. Additional testing showed that her vitamin C level was <3 umol/L. Following stabilisation, high-dose vitamin C therapy was initiated. Subsequently, she showed continued clinical improvement and remained asymptomatic upon her discharge. Discussion: While uncommon, it is crucial to investigate vitamin C deficiency when confronted with an unexplained haemorrhagic pericardial effusion, particularly in patients with risk factors. Conclusion: Our case highlights the significance of early detection of this condition in promptly addressing the diverse complications of scurvy, thereby enhancing the prognosis of a potentially fatal condition. LEARNING POINTS: Haemorrhagic pericarditis could be an initial indication of scurvy.Vitamin C deficiency must be included in the differential diagnostic of haemorrhagic tamponade, even in the absence of a typical signs and symptoms of scurvy.

Scurvy: Rediscovering a Forgotten Disease.

Scurvy is a nutritional deficiency caused by low vitamin C levels that has been described since ancient times. It leads to a varied presentation, affecting multiple organ systems due to its role in the biochemical reactions of connective tissue synthesis. Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. Although there has been a dramatic reduction in the prevalence of scurvy in modern times owing to vitamin C supplementation and intake, sporadic cases still occur. In developed countries, it is mainly diagnosed in the elderly and malnourished individuals and is associated with alcoholism, low socio-economic status, and poor dietary habits. Scurvy has been an unusual cause of gastrointestinal (GI) bleeding among other GI manifestations. It can be adequately treated and prevented via vitamin C supplementation.

Abdominal Ecchymosis: Emergency, or Urgen-C?

Scurvy is a multisystem disease caused by vitamin C deficiency, historically associated with lethargy, gingivitis, ecchymosis, edema, and death if left untreated. Contemporary socioeconomic risk factors for scurvy include smoking, alcohol abuse, fad diets, mental health conditions, social isolation, and economic marginalization. Food insecurity is also a risk factor. This report describes a case of a man in his 70s who presented with unexplained dyspnea, abdominal pain, and abdominal ecchymosis. His plasma vitamin C level was undetectable, and he improved with vitamin C supplementation. This case highlights the significance of awareness of these risk factors and emphasizes the need for a comprehensive social and dietary history to enable the timely treatment of this rare but potentially fatal disease.

A Reversible Cause of Cutaneous Rash in a Patient With Alcohol Consumption.

The most common cutaneous manifestations of alcoholism include urticarial reaction, flushing, porphyria cutanea tarda, psoriasis, rosacea, seborrheic dermatitis, and pruritus. Here, we present a case of a young male with a history of alcohol abuse who presented with non-blanching, petechial, and perifollicular macular rash secondary to vitamin C deficiency in view of poor oral intake. The rash improved significantly with vitamin C supplementation. Although rare in developed countries, clinicians should keep vitamin C deficiency as a differential diagnosis for skin rash in alcohol consumers.

Rheumatologic manifestations with elevated levels of IL-6, IL-17A, and IL-23 in a patient with scurvy.

Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4 months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.

Scurvy: Rare Orthopaedic Complications Associated with Multinutritional Deficiencies.

Suboptimal nutrition can lead to deficiencies in micronutrients such as ascorbic acid (vitamin C), which can present with catastrophic neurological sequelae. Deficiencies of vitamin C, vitamin B3 (niacin) and zinc levels contribute to reduced bone density. Vitamin C associated vertebral fractures, although rare in adults, are still treatable if diagnosed early with a thorough clinical and nutritional history, and early supplementation. Radiological clues suggestive of scurvy-induced vertebral fractures can be diagnosed on plain X-ray and MRI spine imaging. LEARNING POINTS: Although nutritional deficits like scurvy, pellagra and zinc deficiency are rare, early recognition and prompt treatment can prevent critical neurological sequelae.Clinical history including nutritional intake and associated patient symptoms are vital to diagnose scurvy-related vertebral fractures, which are treatable.It is important to note that scurvy can also present in an adult population.

Scurvy in children - A neglected disease?

BACKGROUND: The incidences of pediatric scurvy has decreased substantially, particularly in developed countries, but there are still reports of it from developing countries. Unusual manifestations have led to delays in diagnosis and treatment. Nevertheless, there are few publications regarding misdiagnosis of scurvy. The objective is to determine dietary factors, clinical manifestations, laboratory and radiologic findings, treatment, and outcomes of scurvy cases. The occurrence of misdiagnosis and its associated factors are also explored. METHOD: The medical records of 0-18 year-old children from 2003 to 2016, diagnosed with scurvy, were included and reviewed. Clinical data, and data regarding feeding history, nutritional status, laboratory and radiologic findings, and misdiagnosis were collected. Univariate and logistic regression analysis were used for identification of the independent associated factors. RESULTS: The study consisted of 106 children. The boys-to-girls ratio was 2.2:1, and their mean age was 44.65 months ± 30.50 months. The common manifestations were refusal to walk, tenderness, and swelling at the lower extremities. Four participants had unusual manifestations including proptosis and scalp hematoma. Low serum vitamin C level and abnormal radiologic findings were detected in most patients. All of them fully recovered after receiving vitamin C supplementation. Misdiagnosis was identified in 74 cases (69%). Logistic regression analysis revealed that temperature higher than or equal to 38 °C, participants aged 3 years or below, and swelling at lower extremities were independently associated with misdiagnosis (adjusted OR 5.91, 3.78, and 3.56 respectively). CONCLUSIONS: Scurvy still exists, and misdiagnosis often occurs. Taking a careful medical history and conducting a physical examination are still the best way to diagnose scurvy.

Scurvy in the Modern World: Extinct or Not?

Scurvy is a nutritional disorder caused by vitamin C deficiency. It was a notorious disease in the ancient world, especially among the sailors, and is of rare occurrence in contemporary, developed countries due to increased access and advancement in nutrition services. Scurvy primarily affects the skin and soft tissue, presenting with a myriad of clinical manifestations ranging from musculoskeletal to bleeding-related complaints and even sudden death in later stages. In this article, we present the case of an elderly female with scurvy-related weakness and gait instability leading to mechanical falls, easy bruising, fatigue, and petechial rash. She had improvement in her constitutional symptoms after the initiation of vitamin C supplements. This case reinforces the need to consider scurvy as one of the differentials for petechial rash and easy bruising apart from bleeding diathesis and vasculitis in the contemporary world, especially in at-risk populations.

Scurvy in Children: The Silent Masquerader.

In modern society, scurvy is well known in its historical perspective rather than clinical relevance. Scurvy is classically thought to manifest with signs of 'bleeding painful gums' in the undernourished. Little is known regarding its ability to mimic a wide range of rheumatological, orthopaedic, neurological and haematological illnesses. Due to the rarity of its occurrence, there is a poor understanding among present-day clinicians, and so scurvy can easily deceive the uninitiated. We report a school-aged boy with normal neurodevelopment who presented with lower limb pain and difficulty in walking. He was seen by multiple specialist doctors before the clinical diagnosis of scurvy was made by a general paediatrician. Investigations showed that this child had X-ray changes typical of scurvy with low serum ascorbic acid levels. On supplementation with vitamin C, he showed dramatic improvement in symptoms and gradually achieved complete recovery.

High-dose vitamin C therapy for symptomatic deficiency in a patient with myasthenia gravis and Crohn's disease.

Vitamin C (ascorbic acid) is an essential water-soluble antioxidant, and deficiency (ie, plasma level <11 µmol/L) can result in scurvy. People at the highest risk for vitamin C deficiency (ie, scurvy) are those with inadequate intake, such as patients with alcohol abuse disorder, malnutrition, psychiatric disorders, restrictive eating habits, and food insecurity, as well as those with malabsorptive syndromes. We present a case of a 26-year-old woman with Crohn's colitis, myasthenia gravis, and juvenile rheumatoid arthritis who presented with frequent bruising, epistaxis, and excessive bleeding from small cuts and who was found to be deficient in vitamin C. Plasma levels initially normalized with oral vitamin C supplementation, but bleeding symptoms eventually returned despite high-dose oral supplementation with 2000 mg daily. She ultimately required routine intravenous supplementation in the home setting for the normalization of levels and the resolution of symptoms. Case reports of vitamin C deficiency typically involve patients with an inadequate intake of vitamin C-containing foods or inadequate absorption. In contrast, our patient reported a regular intake of vitamin C-containing foods, in addition to oral supplementation, but continued to have difficulty maintaining normal vitamin C levels. Scurvy should be considered for any patient with symptoms of bleeding, petechiae, or ecchymosis and, although it can typically be treated with oral vitamin C, intravenous repletion may be necessary in some cases.

Spontaneous retrobulbar hemorrhage in the setting of warfarin therapy and latent scurvy diagnosis.

We present a case of spontaneous nontraumatic retrobulbar hemorrhage associated with anti-coagulation therapy and a new diagnosis of scurvy. A 68-year-old male on chronic anti-coagulation therapy presented with a retrobulbar hemorrhage requiring urgent canthotomy and cantholysis. Despite the absence of a supratherapeutic INR and normal clotting factors, the patient continued to have spontaneous hemorrhages within the orbit and elsewhere. Workup revealed a severe vitamin C deficiency consistent with scurvy. Further investigation of dietary history demonstrated an avoidance of all citrus fruit upon starting warfarin due to misunderstanding in medication counseling on avoidance of grapefruit. With repletion of vitamin C and further medication counseling, the patient had no further episodes of spontaneous hemorrhage.