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.

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.

Scurvy and vitamin C deficiency in an Australian tertiary children's hospital.

AIM: We aimed to investigate the frequency of vitamin C deficiency scurvy in the Australian paediatric context, describe cohorts at risk, and identify factors associated with development of symptoms in children with vitamin C deficiency. We also aimed to propose a management guideline for children with features of scurvy. METHOD: A retrospective study was done at a tertiary paediatric hospital in Australia over a three-year period, from August 2019 to July 2022. Children from birth to 18 years old, whose vitamin C levels were low (<23 µmol/L), were included. Data extracted from hospital medical records included demographics, weight, co-morbidities, eating disorder diagnoses, clinical features, investigations and treatment. Descriptive statistics and risk statistics were performed. RESULTS: In a cohort of 887 patients who had their vitamin C levels checked, we identified 272 (31%) who had a vitamin C level <23 µmol/L. Of these, 13 (5%) were symptomatic of vitamin C deficiency and 19 (7%) may have been symptomatic. In patients with vitamin C deficiency, 248 (91%) had comorbidities, neurodevelopmental disorders being most common, and 176 (65%) had restricted eating. When the asymptomatic and symptomatic groups were compared, in the symptomatic group, there was a significantly lower vitamin C level and disordered eating related to autism spectrum disorders was more common. CONCLUSION: In order to avoid delayed diagnoses and unnecessary investigations, clinicians should be familiar with symptoms of scurvy and perform a dietary assessment, vitamin C assay, and commence empiric vitamin C supplementation where appropriate.

Pictorial review: challenges in distinguishing bilateral metaphyseal marrow abnormalities on magnetic resonance imaging.

The paediatric metaphysis is afflicted by a wide range of pathological processes as it is the most metabolically active and well-vascularised part of the developing skeleton. This review focuses on metaphyseal marrow signal change detected with magnetic resonance imaging, which is most often occult on radiographs. When bilateral, these imaging appearances frequently present a diagnostic quandary. This review assists the radiologist to confidently dismiss physiological signal change and confidently work through the differential diagnosis. This is achieved by illustrating a practical method of classifying signal change into four categories: physiological red marrow, red marrow reconversion, marrow infiltration, and oedema-like marrow signal intensity. In doing so, various pathological entities are reviewed along with imaging pearls and next-step investigations.

Medical aspects of the tour by Martin Martin (c 1660-1719) of the Western and Northern Islands of Scotland, Circa 1695.

This review is based investigations on the Western Isles, Scotland, by Martin Martin, a notable Scottish Highlander, academic and medical doctor, of the 17th-18th century. His extensive observations of the geography and peoples of these Isles were recorded in his books, "On the Description of the Western Islands of Scotland Circa 1695" and "A Late Voyage to St Kilda". In these books and subsequent papers there were some noteworthy observations on the occurrence (and as he says non-occurrence) of "epidemical" diseases and conditions afflicting the peoples of The Isle of Skye and the Western Isles of Scotland in this period, and these are discussed in this review. Martin also gives details of a wide variety of remedies that were observed or reported by inhabitants around that time. Some of these remedies are interesting for their relevance to the period but others are of doubtful merit. These are reviewed here more for their significance in the understanding of the diseases and conditions of humans and even in some cases animals at that time. Introductions by Charles Withers and R.W. Munro, 11 and re-assessments of the contributions of Martin and colleagues of that time have given insight into the health and condition of peoples of the Western Isles of Scotland(the Occidental) (Martin 1695; Martin 1716).

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.

Unwinding the potentials of vitamin C in COVID-19 and other diseases: An updated review.

Background: The discovery of vitamin C (ascorbic acid) is related to the ancient history of persistent research on the origins of the haemorrhagic disease scurvy. Vitamin C is an important nutrient that aids in a variety of biological and physiological processes. Scientists have been researching the function of vitamin C in the prevention and ailment of sepsis and pneumonia for decades. This has created a potential platform for applying these results to individuals suffering from severe coronavirus infection (COVID-19). Vitamin C's ability to activate and enhance the immune system makes it a promising treatment in the present COVID-19 pandemic. Vitamin C also aids in the activation of vitamin B, the production of certain neurotransmitters, and the transformation of cholesterol into bile acids. Hence, vitamin C is used for the treatment of many diseases. Aim: This review highlights the Vitamin C investigations that are performed by various researchers on patients with COVID 19 infection, the clinical studies and their observations. The authors have additionally updated information on the significance of vitamin C insufficiency, as well as its relevance and involvement in diseases such as cancer, wound healing, iron deficiency anaemia, atherosclerosis and neurodegenerative disorders. Here, we discuss them with the references. Methods: The method used in order to perform literature search was done using SciFinder, PubMed and ScienceDirect. Results: There is a potential role of vitamin C in various diseases including neurodegenerative disorders, COVID-19 and other diseases and the results are highlighted in the review with the help of clinical and preclinical data. Conclusion: More research on vitamin C and the undergoing clinical trials might prove a potential role of vitamin C in protecting the population from current COVID-19 pandemic.

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 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.

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.

Suspicion of Munchausen syndrome by proxy with a child's presentation of undernutrition, scurvy, and an apparent Avoidant Restrictive Food Intake Disorder.

PURPOSE: Avoidant Restrictive Food Intake Disorder (ARFID) was recently characterized in the DSM-5 classification. Potential differential diagnoses remain poorly reported in the literature. Our purpose was to present a possible Munchausen syndrome by proxy with undernutrition and scurvy, presenting as ARFID in a child. METHODS: We describe here a case of an 8-year-old boy who presented with severe undernutrition (BMI = 11.4) and scurvy leading to joint pains. The boy had had a very selective diet since early childhood, and his condition required hospitalization and enteral refeeding. Because of his specific eating behaviour, an ARFID was initially suspected. However, observation of the mother-child relationship, analysis of the child's eating behaviour, and retrospective analysis of his personal history suggested that this was not a true ARFID, and that the selective eating behaviour had probably been induced by the mother over many years, who probably maintained a low variety diet. CONCLUSION: Munchausen syndrome by proxy is a difficult differential diagnosis, which may also affect patients with ARFID symptoms, which may also present in the affected child as apparent ARFID. LEVEL OF EVIDENCE: Level V, descriptive study.

Scurvy in a Pediatric Patient With Autism and Limp: A Case Report.

BACKGROUND: Limping is a common chief complaint in the pediatric emergency department (ED) and can be difficult to assess in pediatric patients, particularly if they have developmental delay. CASE REPORT: We present a case of a 5-year-old male with nonverbal autism who presented with a progressive limp, weakness, pain, and rash over the course of 1 month. A magnetic resonance imaging scan of the pelvis performed while the patient was sedated revealed multifocal osseous marrow signal abnormalities, ultimately consistent with vitamin C deficiency or scurvy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Scurvy can present with nonspecific limp, rash, and bony pain and should be considered in pediatric patients with developmental/sensory delay who may restrict their diets. Emergency physicians should broaden their differential diagnoses to nutritional deficiencies such as scurvy in the evaluation of pediatric patients with limp.

Child with prolonged leg pain and bruising.

A 12-year-old boy was admitted to the paediatric ward with a 4-month history of worsening pain and bruising to his legs, which had resulted in a progressive reduction in his mobility. He initially had had difficulty weight bearing, which had then progressed further making him wheelchair bound. On examination, there was extensive bruising (figure 1) to his oedematous legs, worse on his right leg compared with his left. His background of autism and 15q13.3 deletion, along with maternal learning difficulties, made deciphering a clear history difficult. However, there was no account of trauma, and he had been afebrile throughout his illness. He had though lost 6 kg in weight but remained clinically stable. He was admitted to the ward for further assessment.

Death in the Arctic - the tragic fate of members of the Franklin expedition (1845).

In May 1845 HMS Terror and HMS Erebus left England under the command of Sir John Franklin to find the Northwest Passage linking the north Atlantic and Pacific Oceans. The ships had been specially equipped for arctic conditions with central heating, auxiliary steam engines and reinforced steel bows to cut through the ice, however, despite these modern additions neither the vessels nor any of the 129 crew members would ever return. Recently the wrecks of the ships have been located in the waters around King William Island, Nunavut, Canada. Numerous theories have been advanced to explain the deaths that involve lead poisoning, scurvy and zinc deficiency. It is most likely, however, that the deaths were the result of multiple factors such as starvation, hypothermia, infection and general physical and mental decline. Cannibalism occurred but whether this involved the use of already dead sailors or the culling of the weak for food is not determinable. The essential point is that the crews were trapped in the Arctic, many thousands of miles from their homes and families, with dwindling food supplies and minimal chances of rescue.

Scurvy Masquerading as Juvenile Idiopathic Arthritis or Vasculitis with Elevated Inflammatory Markers: A Case Series.

Ten patients with scurvy were evaluated by rheumatology; we review their clinical, laboratory, and dietary presentations. Eight patients had developmental delay or autism. All had elevated inflammatory markers. These clinical and laboratory features with imaging findings can mimic rheumatic conditions such as arthritis, vasculitis, and chronic nonbacterial osteomyelitis (CNO).

No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers.

PURPOSE: Scurvy, due to vitamin C deficiency, is commonly referenced as a "forgotten" or "historical" disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases. CASE DESCRIPTIONS: Case one occurred in a 12-year-old non-verbal, non-ambulatory female on a ketogenic diet for refractory epilepsy. Clinical findings included hemarthrosis, transfusion dependent anemia, elevated inflammatory markers, and epiphysiolysis. Magnetic resonance imaging (MRI) revealed multi-focal bone marrow signal abnormalities and physeal irregularities. Case two occurred in a typically developing 5-year-old male presenting with limp and knee pain. Symptoms progressed despite casting and immobilization. Mild anemia, elevated inflammatory markers, and multi-focal marrow and physeal MRI abnormalities were identified. Subsequent dietary history revealed total absence of fruit or vegetable consumption. The diagnosis of scurvy was confirmed in both cases by undetectable plasma vitamin C concentrations. Treatment with vitamin C led to rapid clinical improvement. CONCLUSION: Scurvy can no longer be considered a historical diagnosis and should not be forgotten when evaluating children with musculoskeletal ailments. Early recognition of the signs, symptoms, and imaging findings of scurvy can reduce the clinical burden of this disease with the timely initiation of vitamin C therapy.

The neuropsychiatric effects of vitamin C deficiency: a systematic review.

BACKGROUND: Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency. METHODS: Relevant studies were identified via systematic literature review. RESULTS: Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified. CONCLUSIONS: Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.

James Cook's first Pacific voyage: alleged scurvy-freedom unmasked.

The east coast of New Holland was discovered 250 years ago during a voyage of covert strategic exploration of the Pacific Ocean regions by Lieutenant James Cook acting under instructions of the Royal Navy espionage chief, Philip Stephens, Secretary of the Admiralty. In addition to the study of the transit of Venus, the well resourced mission included some clandestine mapmaking during August 1768 to July 1771. Tasked by the Royal Society of London to investigate the anti-scorbutic effects of a variety of foods and herbs, Cook's post-operational debrief to the Admiralty included the inaccurate supposition that HM Bark Endeavour's cruise was scurvy-free. Why did Cook extend deceptive cartographic practices deliberately to conceal the apparent failure of the anti-scorbutic comestibles?

Childhood Scurvy: A Nearly Extinct Disease Posing a New Diagnostic Challenge, a Case Report.

Scurvy is seldom encountered in modern day clinical practice. Children can present with nonspecific features which can mimic several other common conditions. We describe here a four-year-old child who presented with severe pain and weakness of bilateral lower limbs and found to be severely malnourished. The diagnosis of scurvy was suspected in the context of underlying malnutrition after excluding other ominous pathologies. Pathognomic radiological changes clinched the diagnosis, and the best supportive evidence was the dramatic response to vitamin C supplementation.