Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports.

BACKGROUND: In the early literature, unintentional vitamin C deficiency in humans was associated with heart failure. Experimental vitamin C deficiency in guinea pigs caused enlargement of the heart. The purpose of this study was to collect and analyze case reports on vitamin C and pulmonary hypertension. METHODS: We searched Pubmed and Scopus for case studies in which vitamin C deficiency was considered to be the cause of pulmonary hypertension. We selected reports in which pulmonary hypertension was diagnosed by echocardiography or catheterization, for any age, sex, or dosage of vitamin C. We extracted quantitative data for our analysis. We used the mean pulmonary artery pressure (mPAP) as the outcome of primary interest. RESULTS: We identified 32 case reports, 21 of which were published in the last 5 years. Dyspnea was reported in 69%, edema in 53% and fatigue in 28% of the patients. Vitamin C plasma levels, measured in 27 cases, were undetectable in 24 and very low in 3 cases. Diet was poor in 30 cases and 17 cases had neuropsychiatric disorders. Right ventricular enlargement was reported in 24 cases. During periods of vitamin C deficiency, the median mPAP was 48 mmHg (range 29-77 mmHg; N = 28). After the start of vitamin C administration, the median mPAP was 20 mmHg (range 12-33 mmHg; N = 18). For the latter 18 cases, mPAP was 2.4-fold (median) higher during vitamin C deficiency. Pulmonary vascular resistance (PVR) during vitamin C deficiency was reported for 9 cases, ranging from 4.1 to 41 Wood units. PVR was 9-fold (median; N = 5) higher during vitamin C deficiency than during vitamin C administration. In 8 cases, there was direct evidence that the cases were pulmonary artery hypertension (PAH). Probably the majority of the remaining cases were also PAH. CONCLUSIONS: The cases analyzed in our study indicate that pulmonary hypertension can be one explanation for the reported heart failure of scurvy patients in the early literature. It would seem sensible to measure plasma vitamin C levels of patients with PH and examine the effects of vitamin C administration.

Pediatric scurvy case report: a novel presentation with deep vein thrombosis secondary to large bilateral spontaneous iliac subperiosteal hematomas.

BACKGROUND: Scurvy is an uncommon disease in developed countries caused by deficiency of vitamin C. We present a case of scurvy in a 14-year-old male with autism with both novel presentation and imaging findings. This case had the novel presentation of lower limb deep vein thrombosis (DVT) secondary to compression of the external iliac vein from large bilateral iliac wing subperiosteal hematomas. Subperiosteal hematoma is a well-recognised feature of scurvy but large and bilateral pelvic subperiosteal hematoma causing DVT has not previously been described. CASE PRESENTATION: A 14 year old Caucasian male with background of autism and severe dietary restriction presented with lower limb swelling and immobility. He was diagnosed with lower limb DVT. Further investigation revealed an iron deficiency anaemia, and he was found on MRI to have large bilateral subperiosteal iliac hematomata causing compression of the iliac vessels. He improved following treatment with vitamin C replacement and follow-up imaging demonstrated resolution of the DVT and hematoma. CONCLUSION: DVT is rare in children and when diagnosed should prompt investigation as to the underlying cause. This case demonstrates an unusual cause of DVT and as an unusual presentation of paediatric scurvy.

Vitamin C Deficiency as a Mimicker of a Coagulation Disorder.

Scurvy is caused by vitamin C deficiency and is often thought of as an ancient malady. However, it still afflicts present-day patients with insufficient nutrition, excessive alcohol consumption and disorders of absorption. Scurvy is traditionally characterised by ecchymosis, petechiae, haemorrhages, poor wound healing, myalgias and arthralgias, but it can also present with non-specific symptoms, including mood changes, fatigue, malaise and dyspnoea. Although scurvy can present with signs of excess bleeding, it does not involve blood clotting. We present a case of concurrent scurvy and pulmonary embolism in which clinical presentation and laboratory findings mimicked a coagulation disorder, resulting in delayed diagnosis and excessive resource expenditure. This case underscores the importance of obtaining an early dietary and substance use history in patients with unexplained haematological symptoms. These crucial components of history-taking can significantly reduce invasive and costly tests, resulting in quicker diagnosis and enhanced patient outcomes.

Orthopaedic Manifestations of Scurvy in an Otherwise Healthy Child from a Low Opportunity Index Neighborhood: A Case Report.

CASE: A 23-month-old otherwise healthy female child from a low opportunity index neighborhood presented with 1 month of lower extremity pain and refusal to bear weight. Radiographic evaluation of bilateral knees revealed lucent metaphyseal bands and a nondisplaced distal femoral metaphyseal corner fracture. A workup identified vitamin C deficiency (scurvy), and the child's symptoms and radiographic abnormalities resolved with vitamin C supplementation. CONCLUSIONS: Scurvy should be considered in children with unexplained musculoskeletal symptoms who may lack access to nutrient-dense foods.

Reversible severe pulmonary hypertension related to scurvy in children.

BACKGROUND: Severe pulmonary hypertension (PH) in childhood is rare and can manifest as a life-threatening episode. We present 2 children with restrictive dietary habits with severe pulmonary hypertension secondary to scurvy and iron deficiency anemia with treatment and outcome. CASE PRESENTATION: The first case is a 2-year-old boy who presented with vomiting, diarrhea, and fever. After rehydration, he had recurrent episodes of hypotension with intermittent abdominal pain. Fluid resuscitation and inotropic medication were given. Then he suddenly collapsed. After 4-min cardiopulmonary resuscitation, his hemodynamic was stabilized. Most of the medical workup was unremarkable except for PH from the echocardiogram with estimated systolic pulmonary artery pressure (PAP) at 67 mmHg. Transient PH was diagnosed, and milrinone was prescribed. Since he had restrictive dietary habits and sclerotic rim at epiphysis in chest films, his vitamin C level was tested and reported low-level result. The second case is a 6-year-old boy with acute dyspnea, a month of low-grade fever, mild cyanosis, and a swollen left knee. Echocardiogram indicated moderate TR with estimated systolic PAP at 56 mmHg (systolic blood pressure 90 mmHg). Milrinone was given. Right cardiac catheterization showed PAP 66/38 (mean 50) mmHg and PVRi 5.7 WU.m2. Other medical conditions causing PH were excluded. With a history of improper dietary intake and clinical suspicion of scurvy, vitamin C was tested and reported undetectable level. Administration of vitamin C in both cases rapidly reversed pulmonary hypertension. CONCLUSION: Pediatric PH related to vitamin C deficiency can manifest with a wide range of symptoms, varying from mild and nonspecific to severe life-threatening episodes characterized by pulmonary hypertensive crises. PH associated with scurvy is entirely reversible with appropriate investigation, diagnosis, and treatment. Our report highlights the importance of considering nutritional deficiencies as potential confounding factors in pediatric PH, emphasizing the need for comprehensive evaluation and management of these patients.

What Do We C in Children With Scurvy? A Case Series Focused on Musculoskeletal Symptoms.

OBJECTIVES: Vitamin C deficiency in children commonly presents with musculoskeletal symptoms such as gait disturbance, refusal to bear weight, and bone or joint pain. We aimed to identify features that could facilitate early diagnosis of scurvy and estimate the cost of care for patients with musculoskeletal symptoms related to scurvy. METHODS: We conducted a retrospective chart review of patients at a single site with diagnostic codes for vitamin C deficiency, ascorbic acid deficiency, or scurvy. Medical records were reviewed to identify characteristics including presenting symptoms, medical history, and diagnostic workup. The Pediatric Health Information System was used to estimate diagnostic and hospitalization costs for each patient. RESULTS: We identified 47 patients with a diagnosis of scurvy, 49% of whom had a neurodevelopmental disorder. Sixteen of the 47 had musculoskeletal symptoms and were the focus of the cost analysis. Three of the 16 had moderate or severe malnutrition, and 3 had overweight or obesity. Six patients presented to an emergency department for care, 11 were managed inpatient, and 3 required critical care. Diagnostic workups included MRI, computed tomography, echocardiogram, endoscopy, lumbar puncture, and/or EEG. Across all patients evaluated, the cost of emergency department utilization, imaging studies, diagnostic procedures, and hospitalization totaled $470 144 (median $14 137 per patient). CONCLUSIONS: Children across the BMI spectrum, particularly those with neurodevelopmental disorders, can develop vitamin C deficiency. Increased awareness of scurvy and its signs and symptoms, particularly musculoskeletal manifestations, may reduce severe disease, limit adverse effects related to unnecessary tests/treatments, and facilitate high-value care.

Unusual case of 'scorbutic proptosis'.

Proptosis is a frequent presenting symptom/sign of many paediatric malignancies. Acute-onset proptosis is an ophthalmic emergency that can endanger vision if not treated promptly. Appropriate treatment must be instituted only after investigating for the underlying aetiology. Here, we report a developmentally delayed boy in middle childhood who presented with recent onset bilateral proptosis. Clinical examination followed by radiological evaluation suggested scurvy to be the underlying cause and vitamin C supplementation led to prompt reversal of proptosis. The relevant literature has been reviewed and presented here to apprise the paediatric oncologists about this rare but easily treatable cause of proptosis.

Infantile scurvy as a consequence of agricultural intensification in the 1st millennium BCE Etruria Campana.

The 1st millennium BCE in Italy was a time of agricultural intensification of staple cereal production which shaped sociocultural, political, and economic spheres of pre-Roman groups. The lifeways and foodways of the Etruscans, the greatest civilization in western Europe before Roman hegemony, are traditionally inferred from secondary written sources, funerary archaeology, archaeobotany, and zooarchaeology. However, no direct data extrapolated from the study of human skeletal remains are available to evaluate the extent to which agricultural intensification and decreased dietary diversity impacted health and the expression of skeletal indicators of metabolic disease. Macroscopic and radiological analyses were conducted on an archaeological skeletal sample of non-adults (n = 29) recovered from Pontecagnano (southern Italy) dating to the Orientalizing period (730-580 BCE). This allowed us to identify five cases of scorbutic non-adults and to assign diagnostic values to skeletal lesions of scurvy that have not been previously described in the literature. The onset of scurvy in the examined sample is related to the increased reliance of Etruscans on crops lacking vitamin C in this period of agricultural intensification. The skeletal expression of scurvy varied among the non-adults, with differences in location and disease severity; these were interpreted considering the age-at-death of the individuals coupled with feeding behaviors and interindividual variability.

Scurvy presenting as difficulty in walking in a child.

Scurvy, a disease caused by ascorbic acid (vitamin C) deficiency, is a rare disease in the modern world. We report a case of a boy in middle childhood, with a background of autism, presenting bed-bound due to progressive bilateral lower limb pain, with concomitant rashes, bleeding gums and worsening lethargy. Detailed dietary history revealed a severely restricted diet. Physical examination showed bilateral lower limb ecchymoses, perifollicular hemorrhages, perifollicular hyperkeratosis and cockscrew hairs which are pathognomonic features of scurvy. A low serum ascorbic acid level confirmed the diagnosis. Therapy with oral vitamin C supplement and rehabilitation with multidisciplinary care was successful, with complete resolution of symptoms. This case emphasises the importance of thorough dietary evaluation in children with autism and food selectivity presenting with non-specific symptoms. Physician awareness of nutritional deficiencies avoids unnecessary extensive investigations and sub-specialty referrals and translates to savings in medical expenses.

Pseudoparalysis Secondary to Vitamin C Deficiency: A Rare Presentation in a Toddler.

CASE: We present a 17-month-old girl with postencephalitic sequelae only on high-calorie cereal milk through a nasogastric tube. She presented with a 3-week history of swelling and decreased lower limb movements. Synovial fluid analysis ruled out septic arthritis. Plain radiograph and magnetic resonance imaging (MRI) were suggestive of scurvy. She was diagnosed to have pseudoparalysis secondary to scurvy. She was started on vitamin C supplements, after which she showed good clinical improvement. CONCLUSION: This case report is to re-emphasize the need for awareness of the possibility of scurvy in children with poor nutritional status due to feeding difficulties.

Scurvy complicated with Capnocytophaga sputigena sepsis as a possible cause of death of king Saint-Louis of France (1270 AD).

The cause of death of Saint-Louis is not known, but recent findings indicated that he presented scurvy and inflammatory jaw disease, which has been associated with infection by oral commensals. Here, we have the exceptional opportunity to analyze the relics of the viscera of King Saint-Louis. A 4.3 g sample from the viscera relics of King Saint-Louis conserved in Versailles' cathedral was subjected to radiocarbon dating, electronic and optic microscopy, and elementary, palynological, molecular, proteomics and microbiological analyses including specific PCR and v3v4 16 S rRNA gene amplification prior to large-scale sequencing using an Illumina MiSeq instrument. The measured radiocarbon age was Cal 1290 CE-1400, which was compatible with that of the viscera of St Louis viscera, considering the addition of lime, incense and vegetables within the human organs. Elemental and palynological analyses confirmed a medieval embalming process. Proteomics analysis identified mainly human muscle and blood proteins. Specific PCR for plague, amoebiasis, shigellosis and typhoid fever was negative. C. sputigena was identified as the main pathogenic species representing 10.8 % of all microbial sequences. In contrast, C. sputigena was found in only 0.001 % of samples sequenced in our center, and the 23 positive human samples showed a dramatically lower abundance (0.02-2.6 %). In the literature, human infections with C. sputigena included odontitis, dental abscess, sinusitis, thoracic infections and bacteremia, particularly in immunocompromised patients with oral and dental diseases consistent with recent analysis of King Saint-Louis' jaw. C. sputigena, a commensal of the mouth that is potentially pathogenic and responsible for fatal bacteremia, may have been the cause of the king's death.

Scurvy: old disease, new lessons.

Scurvy, the condition associated with severe vitamin C deficiency, is believed to be one of the oldest diseases in human history. It was particularly prevalent during the Age of Sail, when long sea voyages without access to fresh food resulted in an epidemic which claimed millions of lives; however, scurvy has existed across time and geography, occurring whenever and wherever diets are devoid of vitamin C. Young children, specifically, were affected by the emergence of 'infantile scurvy' in the 19th century owing to the use of heated milk and manufactured infant foods of poor nutritional quality. Scurvy continues to occur in at-risk groups. In children and youths, it is primarily observed in the context of autism spectrum disorder and feeding problems such as a limited food repertoire and high-frequency single food intake. Diagnosis may be delayed and invasive testing undertaken owing to clinicians' lack of familiarity with the disease, or the mistaken assumption that it is exclusively a disease of the past. The aetiology, clinical manifestations and treatment of scurvy are described. Its long history and current epidemiology are also reviewed, demonstrating that scurvy is very much a disease of the present. It is suggested that future efforts should focus on (i) anticipatory guidance and early nutritional intervention, informed by an understanding of scurvy's epidemiology, with the aim of preventing the disease in those at risk, and (ii) prompt recognition and treatment to minimise morbidity and healthcare costs.Abbreviations: ASD: autism spectrum disorder.

Investigation of an outbreak of disease compatible with scurvy in a male penitentiary in the state of Ceará, Brazil, 2019-2020: a case-control study.

MAIN RESULTS: An outbreak of illness compatible with scurvy occurred among male prison inmates; most frequent signs/symptoms were edema and pain in lower limbs, difficulty in walking and hematoma/ecchymosis; the associated factor was age > 40 years. IMPLICATIONS FOR SERVICES: The results can contribute to the identification and description of scurvy outbreaks in other contexts and territories. Epidemiological studies of events like this enhance the practice of field epidemiology in health services. PERSPECTIVES: It is expected that the prevention of hypovitaminosis, such as scurvy, will be based on public policies aimed at the population deprived of liberty; and that the capabilities of health services to detect and respond to cases of the disease will be improved. OBJECTIVE: to identify the occurrence of an outbreak compatible with scurvy and exposure factors associated with typical signs/symptoms of hypovitaminosis that occurred in a male penitentiary in Ceará, Brazil between 2019-2020. METHODS: this was a population-based case-control study; we used clinical records and interviews with compatible cases - based on sign/symptom onset during the study period - and with controls; we carried out multivariate analysis. RESULTS: out of 62 cases, mean age was 40.6 years (SD = 10.8); main signs/symptoms were edema and pain in the lower limbs (100.0%), difficulty in walking (91.9%), hematoma/ecchymosis in the lower limbs (90.3%) and fever (88.7%); we identified being over 40 years old as an associated factor (aOR = 1.10; 95%CI 1.05;1.17; p-value = 0.001); and as protective factors: working (aOR = 0.11; 95%CI 0.03;0.36; p-value < 0.001) and taking part in classes (aOR = 0.21; 95%CI 0.08;0.59; p-value = 0.003) in the prison. CONCLUSION: we considered the penitentiary outbreak to be compatible with scurvy due to characteristic signs/symptoms, associated with the identified factors; we recommended regular provision of a diet rich in vitamin C to all male inmates and clinical follow-up of cases.

Scurvy and food selectivity in childhood: a case report.

Despite its rarity, symptomatic micronutrient deficiency remains a public health problem. Scurvy is the differential diagnosis for bleeding disorders and hematological and rheumatological diseases, especially in patients with eating disorders. However, it is unrelated to autism spectrum disorders or other neurodevelopmental disorders. A previously healthy 10-year-old boy living in São Paulo, Brazil, had a history of significant food selectivity unrelated to autism spectrum disorder, resulting in symptomatic ascorbic acid deficiency (scurvy). This resulted in pain and purpuric lesions on the lower limbs, gingival edema, bleeding during tooth brushing, asthenia, weakness, malaise, and sadness. Therefore, dietary anamnesis is important for routine monitoring of child growth and development. This process helps prevent nutritional deficiencies, facilitates early diagnosis of eating disorders, and enables multidisciplinary follow-up for these patients.

Deficiency diseases in the Kyiv Rus' subadult population: The issue of the small sample effects.

This paper underlines the importance of the small sample effects consideration in paleopathological research providing an example of children from Kyiv Rus' cemeteries dated to the 10th-13th century AD. The study presents data introduction and systematization, i.e., construction of the statistically significant disease profiles combining the analyzed sites according to the distribution of anemia, scurvy, and rickets. Then we present usually provided (often 'associative') interpretations for the obtained results and question their reliability from the perspective of the small samples effects. This leads to the discussion of explanatory limits of bioarcheological research basing on the small sample analysis.

Unusual Presentation of Pediatric Scurvy: A Necrotic Gastrostomy Tube Site in a 14-Year-Old Boy.

BACKGROUND Despite being considered a disease of the past, pediatric scurvy is increasingly reported in developed countries, especially among children with autism spectrum disorder, developmental delays, or a restrictive diet. Pediatric patients typically present with lower extremity pain or refusal to walk. This case study features an atypical presentation of scurvy in a non-ambulatory patient. CASE REPORT A 14-year-old boy with arthrogryposis multiplex congenita displayed a late-stage scurvy symptom: a necrotic gastrostomy tube site, indicative of poor wound healing due to vitamin C deficiency. The usual telltale symptoms of scurvy were camouflaged due to his non-ambulatory status, which may have contributed to a delayed presentation. Nevertheless, a comprehensive clinical evaluation, incorporating diet history, gingival symptoms, petechiae, and characteristic radiological signs, eventually led to the correct diagnosis. Although acute osteomyelitis was initially suspected, it was subsequently ruled out. Upon initiation of vitamin C therapy, the patient's symptoms subsided within a few days, and the necrotic tissue surrounding the gastrostomy tube healed completely within two weeks. CONCLUSIONS The highlighted case underscores the importance of including scurvy in the differential diagnosis for pediatric patients with lower extremity pain without fever. A detailed dietary history focusing on vitamin C intake is crucial during clinical evaluation. Early initiation of vitamin C therapy, when scurvy is suspected, may prevent unnecessary and extensive diagnostic workup for other potential causes, offering timely relief to the patient.