Scurvy and Tinea Corporis Simulating Leukocytoclastic Vasculitis.

ABSTRACT: Leukocytoclastic vasculitis (LCV) is a small vessel inflammatory condition considered to be caused by circulating immune complexes and often occurs after an acute infection or exposure to a new medication, although it may be associated with an underlying systemic disease or be idiopathic in nature. It is important to determine the etiology, identify the extent of the disease for early intervention and appropriate management, and treat and/or eliminate the underlying cause. Here, we report cases of scurvy and tinea corporis that presented with histopathologic features of LCV and had significant clinical improvement with treatment of the underlying etiologies. These cases emphasize that histopathologic features of early evolving LCV may be seen in other settings including scurvy and tinea corporis. Appropriate treatment of the underlying condition is important for optimized patient management.

Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.

Endoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1α, ERO1ß, and PRDX4 compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly modest delay in disulfide bond formation in secreted proteins but a profound, 5-fold lower procollagen 4-hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice, and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H(2)O(2)-generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation, and a noncanonical form of scurvy.

Scurvy, an old story in a new time: The hematologist's experience.

BACKGROUND: Scurvy is a rare entity in developed countries and the diagnosis may often be delayed resulting in unnecessary investigations and/or potentially severe complications. A recent increase in the number of patients diagnosed with scurvy in our hematology clinics indicated the need to review the literature on the diagnosis and optimal management of similar patients. METHODS: We conducted a retrospective chart review of patients referred to hematology at our tertiary care centre between 2010 and 2018, who were ultimately diagnosed with scurvy. Data collected from electronic medical records included baseline characteristics, clinical features on presentation, bloodwork results from initial consultation, treatment plan as well as response to treatment. FINDINGS: Twenty-two adults patient had a diagnosis of scurvy with a mean vitamin C level of 6 µmol/L. Iron deficiency anemia (54%) and gastrointestinal disorders (54%) were the most common comorbidities noted in our cohort. Proton-pump inhibitors use was noted in 54% of patients. Bleeding (45%) and bruising (45%) were the most commonly reported clinical features. Eleven patients received oral supplementation, five had intravenous (IV) vitamin C and six were not treated. Two patients required a transition from oral to IV supplementation. Vitamin C dosing ranged between 250 and 2000 mg and the frequency varied from daily for oral therapy to every few weeks or months for IV. INTERPRETATION: Awareness of scurvy and its associated risk factors and clinical presentation is important in the evaluation of a patient with bleeding tendency. Treatment plan should be individualized, and a careful review of patients' diet, medial history and medications is warranted.

[Cutaneous manifestations of nutritional deficiencies]. / Manifestations cutanées de carences nutritionnelles, ou quand l'examen de la peau alimente le diagnostic.

In elderly or chronically ill patients, nutritional deficiencies are common and the presence of related skin lesions is not unusual. Recognition of such cutaneous involvement is important regarding the diagnosis essentially based on clinical elements. By using some clinical case reports, we will describe several pathologies related to nutritional deficiencies like scurvy, pellagra and acquired acrodermatitis enteropathica.

Dans nos populations de patients vieillissants ou atteints de maladies chroniques, les carences nutritionnelles sont fréquentes et la présence de manifestations dermatologiques associées n'est pas rare. La reconnaissance de telles atteintes cutanées est importante pour le diagnostic qui est essentiellement clinique. A l'aide de vignettes cliniques, nous allons discuter ici de pathologies carentielles comme le scorbut, la pellagre ainsi que l'acrodermatite entéropathique acquise.

Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide.

The past two decades have seen a proliferation in bioarchaeological literature on the identification of scurvy, a disease caused by chronic vitamin C deficiency, in ancient human remains. This condition is one of the few nutritional deficiencies that can result in diagnostic osseous lesions. Scurvy is associated with low dietary diversity and its identification in human skeletal remains can provide important contextual information on subsistence strategy, resource allocation, and human-environmental interactions in past populations. A large and robust methodological body of work on the paleopathology of scurvy exists. However, the diagnostic criteria for this disease employed by bioarchaeologists have not always been uniform. Here we draw from previous research on the skeletal manifestations of scurvy in adult and juvenile human skeletal remains and propose a weighted diagnostic system for its identification that takes into account the pathophysiology of the disease, soft tissue anatomy, and clinical research. Using a sample of individuals from the prehistoric Atacama Desert in Northern Chile, we also provide a practical example of how diagnostic value might be assigned to skeletal lesions of the disease that have not been previously described in the literature.

The epigenetic role of vitamin C in health and disease.

Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.

Lost at Sea in Search of a Diagnosis: A Case of Unexplained Bleeding.

Scurvy results from a dietary deficiency of vitamin C (ascorbic acid) and is rarely thought of in modern day medicine. It now almost always occurs in pediatric patients with behavioral diagnoses, nutritionally restricted diets, and food allergies. Symptoms of scurvy include ecchymoses, bleeding gums, and arthralgias. Here, we present a 17-year-old male with autism spectrum disorder and a diet severely deficient in ascorbic acid due to textural aversion and food preferences. He presented with recurrent arthritis, hemarthrosis, bruising, and anemia. His vitamin C level was low, and his symptoms improved promptly after treatment with ascorbic acid.

Assessment of diet and recognition of nutritional deficiencies in paleopathological studies: A review.

An essential part of paleopathology is the study of diet and nutrition as well as inferring aspects of diet and nutrition from the skeletal pathology. Interpretation of nutritional and metabolic disease-related pathologies often provides additional insight into the daily social and cultural practices of people. However, precise diagnoses of specific vitamin-related deficiencies in archaeological skeletal remains are still quite problematic and specific diagnoses are rarely possible. This partly stems from the fact that many nutritional or metabolic diseases do not necessarily result in an osteological response and when they do, the comorbidity and analogous osteological responses to vitamin deficiencies may hamper the definite diagnosis of nutrition-related disease. Clin. Anat. 29:862-869, 2016. © 2016 Wiley Periodicals, Inc.

Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II.

Humans and guinea pigs are unable to produce vitamin C, with deficiency resulting in a well-known disorder of collagen synthesis. Pial basement membrane structure preservation is essential in the proper migration of neurons. In our study, intrauterine deprivation of vitamin C in guinea pig fetuses led to a collagen synthesis disorder, weakness, and finally a breach of pial basement membrane. We found excessive migration of the external germinal layer cells into the subarachnoid space of the cerebellum through defects in the pial basement membrane. The changes ranged from focal rupture of pial basement membranes to their complete disintegration. The loss of proper folia formation resulted in macroscopically visible flattening of the cerebellar surface. Different grades of dysplastic changes in the folia of the cerebellar cortex were observed in 2 experimental groups assigned different limits to mark the time of commencement and duration of vitamin C deprivation. The most severe form of dysplastic changes was characterized by marked irregularity of the cerebellar cortex similar to that in lissencephaly type II. Thus, prenatal vitamin C deficiency represents a novel animal model to study the effects of collagen synthesis on development of breaches in the pial basement membrane, disordered migration of neurons, dysplasia of cerebellar cortex, and the pathogenesis of lissencephaly.

MRI findings in pediatric patients with scurvy.

In modern times scurvy is a rarely encountered disease caused by ascorbic acid (vitamin C) deficiency. However, sporadic cases of scurvy persist, particularly within the pediatric population. Recent individual case reports highlight an increased incidence of scurvy among patients with autism or developmental delay, with isolated case reports detailing the magnetic resonance imaging (MRI) findings of scurvy in these pediatric populations. We present the MRI findings of scurvy in four patients with autism or developmental delay, and review the literature on MRI findings in pediatric patients with scurvy. Despite its rarity, the radiologist must consider scurvy in a pediatric patient with a restricted diet presenting with arthralgia or myalgia.

A likely case of scurvy in a rural Early Classic Maya burial from Actun Uayazba Kab, Belize.

A Maya burial of a late adolescent (Burial 98-3) found in the rockshelter entrance of Actun Uayazba Kab (AUK), Belize, displays a combination of lesions that is consistent with scurvy. Signs include large, active lesions on the posterior surfaces of maxilla; relatively mild porotic hyperostosis along the midline of the skull on the parietals and occipital; cribra orbitalia; potential pinprick lesions on the greater wings of sphenoid and temporal; reactive lesions on the palate, temporal lines of frontal and parietals, and external and internal surfaces of zygomatics; small lesions on the popliteal surfaces of both femora; and periodontal disease. Identification of scurvy at AUK potentially informs the analysis of other primary burials and scattered bone found there and at other nearby sites, which often reveal evidence of nonspecific lesions that are usually attributed to anemia and infection, but that are also consistent with scurvy. The social and ecological context of this Protoclassic (0-AD 300) individual, who lived in a rural agricultural community with no evidence of complex social hierarchy, contrasts with typical discussions of disease among the Maya, which tend to focus on the degrading effects of overcrowding and resource deficiencies. While scurvy has been largely overlooked in the Maya area, this study supports earlier arguments for its presence that were based largely on clinical and ethnographic analogies and suggests the need to incorporate scurvy into broader synergistic models of ancient health.

A macroscopic assessment of porosity and new bone formation on the inferior pars basilaris: Normal growth or an indicator of scurvy?

OBJECTIVES: This research aims to determine the aetiology of porosity and subperiosteal new bone formation on the inferior surface of the pars basilaris. MATERIALS: A total of 199 non-adult individuals aged 36 weeks gestation to 3.5 years, from a total of 12 archaeological sites throughout the UK, including Iron Age (n=43), Roman (n=12), and post-medieval (n=145) sites, with a preserved pars basilaris. METHODS: The pars basilaris was divided into six segments, with porosity (micro and macro) and subperiosteal new bone formation recorded on the inferior surface in scorbutic and non-scorbutic individuals. Scurvy was diagnosed using criteria from the palaeopathological literature that was developed using a biological approach. RESULTS: There was no statistically significant difference in microporosity between scorbutic and non-scorbutic individuals in four out of the six segments analysed. There was a significant negative correlation between age and microporosity in non-scorbutic and scorbutic individuals. A significant difference in subperiosteal new bone formation was observed between scorbutic and non-scorbutic individuals. CONCLUSIONS: Microporosity on the inferior pars basilaris should not be considered among the suite of lesions included in the macroscopic assessment of scurvy in non-adult skeletal remains (less than 3.5 years). SIGNIFICANCE: This study highlights the risk of over diagnosing scurvy in past populations. LIMITATIONS: It is difficult to distinguish between physiological (normal) and pathological (abnormal) bone changes in the skeleton of individuals less than one year of age. SUGGESTIONS FOR FURTHER RESEARCH: Future research should focus on the analysis of individuals over 3.5 years of age.

Evidence of non-adult vitamin C deficiency in three early medieval sites in the Jaun/Podjuna Valley, Carinthia, Austria.

OBJECTIVE: This study aims to determine and discuss the prevalence of non-adult scurvy cases from the early medieval Jaun/Podjuna Valley in southern Austria. MATERIALS: 86 non-adult individuals were assessed from three early medieval sites. METHODS: Morphological characteristics associated with suggestive and probable scurvy were observed macroscopically and under 20-40x magnification. RESULTS: A significant relationship between the prevalence of scurvy and age group was observed. Perinates (46%, 6/13) and children (27.5%, 8/28) showed a high prevalence of skeletal features indicating a diagnosis of scurvy, while no cases of scurvy were observed in adolescents and adults. CONCLUSIONS: In this Alpine region, scurvy occurred frequently in infants and children. Seasonal fluctuations of diet are discussed as factors triggering scurvy. SIGNIFICANCE: This study sheds new light on the prevalence of scurvy in the Alpine region and how the region developed after the fall of the Roman Noricum. It also models ways in which multiple lines of evidence can contribute to the diagnostic process. LIMITATIONS: Poor preservation posed a challenge to identifying probable cases of scurvy. Likewise, non-adult remains are difficult to diagnose due to their developing nature and it is not always possible to distinguish between normal bone growth and pathological growth. SUGGESTIONS FOR FURTHER RESEARCH: Future applications of biomolecular studies will help illustrate changes in diet that may have contributed to vitamin deficiencies.

A Prehispanic infant from Tenerife with diffuse microporotic lesions.

We describe diffuse microporotic lesions observed in most of the scattered skeletal remains belonging to a ≈ 6 months-old female (genetic sexing) prehispanic (antiquity ≈ 600 years BP) individual recovered from a small recess of a basaltic burial cave in the highlands (2300 m above sea level) of Tenerife. Although sphenoid wings were lacking, microporotic lesions were present in several bones, especially in the hard palate, basilar part of the occipital bone, outer aspect of the maxilla, and proximal half of the right humerus, accompanied by a subtle periosteal reaction. Although non-specific, bone lesions may be compatible with scurvy, possibly in the context of malnutrition, that probably also affected the mother, given the young age of the infant and her dependence on maternal feeding. Pathophysiological connections among iron deficiency, vitamin C deficiency and vitamin D deficiency are discussed. Both observational reports on paleopathological cases of diffuse microporotic lesions as well as experimental studies devoted to discern the relative and combined effects of hypoxia-mediated bone marrow expansion, protein-calorie malnutrition, ascorbate, vitamin D or iron deficiency on such lesions are needed.

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.

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.

Manifestation of infantile scurvy in a skeleton from the high medieval village of Trutmanice (South Moravia, Czech Republic).

The study describes the pathological findings recorded on the human remains of a 3 to 4-year-old child found in the burial site of Trutmanice (Czech Republic), dated to the 13th-15th century. The human remains were examined using standard macroscopic osteological and paleopathological methods, supplemented by radiographic examination. Although the preservation of the bones limited the analysis, multiple pathological changes were observed mainly on the skull: cribra orbitalia, small pores and fine deposits of newly formed bone tissue, hypertrophic diploë, grooves indicating rich branching of meningeal arteries on the intracranial surface of the cranial vault. A very fine periostotic deposition of newly formed bone tissue was also observed at the distal end of the diaphysis of the right tibia and both distal ends of the femora. The radiographs of the femora showed white lines of Frankel, scurvy lines, and Wimberger's rings. The observed pathological changes were possibly consistent with scurvy based on differential diagnosis. Reports about cases of juvenile scurvy from rural areas within the context of landlocked countries of Central Europe are rare. While scurvy is now more frequently reported in the paleopathological literature, evidence for scurvy within one of the most natural agricultural areas in the Czech lands remains rare. We recommend using radiographic examination to complement the diagnosis of scurvy in future paleopathological and epidemiological studies of past populations.