|DIETARY SOURCES OF VITAMIN C AND CLASSIC CUTANEOUS MANIFESTATIONS OF SCURVY|
Scurvy is a well-known nutritional disease that results from a lack of the water-soluble vitamin, ascorbic acid (vitamin C). Scurvy has a well-documented history. It was first recognized in the fourteenth century in sailors who spent long amounts of time at sea. The symptoms were recognized as being related to a lack of fresh foods, especially citrus products. In 1753, James Lind, a British surgeon aboard the HMS Salisbury, performed the first documented clinical trial proving that scurvy was caused by a lack of citrus fruit in the diet of sailors. After Lind’s discovery, citrus fruits were included in ships’ provisions, and the incidence of scurvy in sailors plummeted. It was not until 1928 that ascorbic acid was isolated by the Hungarian chemist, Albert von Szent-Grörgyi, who was eventually awarded the Nobel Prize for this discovery. Scurvy is still present in some areas of the world due to inadequate dietary intake of vitamin C. Scurvy is uncommon in North America but can be seen in individuals with abnormal diets.
Clinical Findings: Scurvy is a disease that can affect a wide range of organ systems. The skin and mucous membranes are always involved and may display the initial symptoms of the disease. Recognition of these symptoms is critical in diagnosing the disease and preventing long-term illness. Scurvy is a rare disease in regions of the world with access to proper dietary intake of vitamin C. In North America and Europe, most cases are the result of abnormal dieting, psychiatric illness, or alcoholism. Prompt recognition of the cutaneous manifestations can lead to treatment and cure of the disease. Scurvy has an insidious onset with nonspecific constitutional symptoms such as generalized weakness, malaise, muscle and joint aches, and easy fatigability with shortness of breath. These symptoms may be related to the macrocytic anemia that is frequently seen in patients with scurvy and is believed to be caused by a coexisting folic acid deficiency.
The first clinical findings are often in the mucous membranes and the skin. There are a multitude of cutaneous manifestations. Early in the course of disease, skin becomes dry and rough, in association with a dulling of the skin tone. Small, hyperkeratotic papules may be noticed and resemble those of keratosis pilaris. More specific and sensitive skin findings then develop, including perifollicular hemorrhage and “corkscrew hairs.” The corkscrew hairs are most noticeable on the extremities. Swan-neck deformity of the extremity hair may also occur due to abnormal bending of the hair; this is less common than corkscrew hair. The nail bed shows splinter hemorrhages. All cutaneous findings appear to be more common on the lower extremities. This is believed to be a result of increased hydrostatic pressure in the lower extremities while one is upright, which leads to increased pressure on the small venules in the follicular locations, resulting in the perifollicular hemorrhages. These findings are also observed in areas of pressure directly on the skin, such as around the waist line. The Rumpel-Leede sign is positive: When a blood pressure cuff is inflated for 1 minute to a value that is greater than the diastolic pressure but less than the systolic pressure, numerous petechial hemorrhages occur distal to and underneath the blood pressure cuff. This test is a sign of capillary fragility induced by increased hydrostatic pressure.
The mucous membranes may show the first sign of the disease. The main finding is edematous, bleeding gums. As the disease progresses, the gums become friable and peel away from the teeth. The teeth may develop dental calculi at the base. This may result in loose teeth and pain. Teeth eventually become disrupted from their attachments and fall out.
Compared with scurvy in adults, congenital scurvy and scurvy during early childhood have unique manifestations related to bony development. Vitamin C is critically important for the development of collagen and cartilage, and abnormalities at a young age result in a variety of bony deformities. Scorbutic rosary is a term given to the prominence of the costochondral junctions. Infants with scurvy develop “frog legs” due to subperiosteal hemorrhage. This form of hemorrhage is painful, and the infant naturally relaxes the lower limbs in this pattern to relieve the pain. Healing of the subperiosteal hemorrhage often involves abnormal calcification of the region and the formation of a more club-shaped bone.
This can lead to difficulty with movement. Radiographs of the long bones reveal the classic white line of Frankel, which represents the abnormal calcification of the cartilage within the epiphysial-diaphysial juncture. The periosteum appears ballooned out due to the presence of subperiosteal hemorrhage. Over time, the hemorrhagic areas become partially or completed calcified.
Infants with scurvy may also develop severe ecchymosis around the eye and in the retrobulbar space, which, when severe, can result in proptosis. Child abuse may be considered in the differential diagnosis.
Breast milk contains adequate amounts of vitamin C, so infantile scurvy is more likely to occur in children who are not breast fed and are given a diet devoid of vitamin C.
Pathogenesis: Vitamin C is an essential vitamin that is acquired through dietary intake. Humans lack the enzyme L-gluconolactone oxidase, which is required for the synthesis of L-ascorbic acid from its precursor, glucose. Dietary sources of vitamin C include fruits, vegetables, and fresh meats. Citrus fruits are the main source of dietary vitamin C. All human tissues contain vitamin C, with the adrenal glands and pituitary glands having the highest concentrations. Leukocytes contain appreciable amounts of vitamin C, and the buffy coat level is helpful in diagnosis. The clinical manifestations of scurvy do not appear until the buffy coat concentration has fallen to less than 4 mg/100 mL or the serum level to less than 20 µmol/L. The normal buffy coat concentration is in the range of 15 to 25 mg/100 mL, and that of the serum is 40 to 120 µmol/L. The kidney has an extraordinary ability to adjust its vitamin C reabsorption and secretion based on serum levels. In scurvy, the kidney salvages all available vitamin C, and the urine concentration is 0 mg/24 hours.
Vitamin C is required as a cofactor for various enzyme functions. Vitamin C supplies electrons to enzymatic reactions. If these are absent, the enzymes are unable to properly produce their intended end product, and the manifestations of scurvy begin to develop. One of the most important functions of vitamin C is to serve as a cofactor, along with ferrous iron (Fe++), for the enzymes prolylhydroxylase and lysylhydroxylase. These enzymes are responsible, respectively, for hydroxylation of the proline and lysine amino acid residues in collagen. If the proper ratio of proline and lysine hydroxylation is not present, the collagen molecule is unable to form a proper triple helix, and its function is compromised. Defective collagen production is the main deficiency responsible for the cutaneous signs of scurvy, because collagen is the major structural protein in blood vessel walls and in the dermis. Vitamin C is also responsible for electron donation in other enzymatic reactions, including those that synthesize tyrosine, dopamine, and carnitine.
Histology: Histology is not required for the diagnosis. Biopsy of a petechial lesion shows perifollicular red blood cell extravasation and a minimal lymphocytic inflammatory infiltrate. If the specimen includes the area around a hair follicle, close inspection will reveal a coiled or corkscrew appearance to the hair follicle. It should be remembered that patients with scurvy have impaired wound healing: After biopsy without proper therapy, the freshly incised skin may take weeks to months to heal, and large ecchymoses typically develop around the biopsy site.
|BONY AND SKIN ABNORMALITIES OF SCURVY|
Treatment: Therapy requires the replacement of vitamin C at a dosage of 300 to 500 mg daily until the symptoms resolve. Then start the recommended daily allowance. Patients show rapid improvement. The root cause must be determined, and if the patient does not respond to therapy, serum levels should be rechecked. If they are still low, noncompliance with therapy should be considered. Often, patients with scurvy have an underlying alcoholism, eating disorder, or psychiatric illness that, if not properly addressed, will continue to occur. Patients should see a nutritionist, who can best educate them on the need for a balanced diet and which foods are high in vitamin C. Alcoholics need to be referred to experts who are adept at treating this common problem. Supplementation with the daily recommended amounts can be continued for life, because any excess vitamin C is not stored in the body but excreted by the kidneys. Supplementation ensures the avoidance of further episodes of scurvy.