Pyridoxine deficiency is a uncommon however identifiable reason behind sideroblastic anemia, melancholy, and peripheral neuropathy. Platinum-based chemotherapy medicine have a structural similarity to pyridoxine, which interferes with the absorption and due to this fact the effectiveness of the drug. If left untreated, it will probably result in irreversible axonal loss and everlasting deficits, resulting in falls. Our case is a really uncommon situation of remoted pyridoxine deficiency presenting as peripheral neuropathy and melancholy as a delayed aspect impact of chemotherapy medicine.
As reported by Barrell et al., peripheral neuropathies embody a variety of issues affecting the peripheral nervous system, together with distal sensory neuropathy, mononeuritis multiplex, polyradiculopathies, and neuropathy leading to nondependent panmodal sensory loss or weak point of the size. . The commonest sample is distal sensory polyneuropathy (DSP), related to length-dependent peripheral nerve harm leading to distal-predominant sensory loss, extreme ache and weak point, leading to gait instability, danger of falling and, in some circumstances, foot ulceration and amputations . Widespread causes of neuropathy embrace diabetes-associated neuropathy and vitamin B12 and folate deficiency. Remoted pyridoxine deficiency presenting as peripheral neuropathy has been sparsely reported in case reviews.
Pyridoxine deficiency is usually related to concurrent deficiencies of different water-soluble nutritional vitamins equivalent to vitamin B12 and folate . Remoted pyridoxine deficiency may be very uncommon in the US. It’s related to circumstances of elevated metabolism equivalent to renal failure on hemodialysis or peritoneal dialysis, autoimmune circumstances equivalent to rheumatoid arthritis and states of decreased consumption/absorption (being pregnant, protein-energy malnutrition, dependence continual alcohol abuse, celiac illness or post-bariatric surgical procedure) .
Presentation of the case
A 67-year-old man offered to our clinic with numbness in his legs as his chief criticism. He first observed it when he was getting a sizzling stone therapeutic massage and could not recognize the warmth on his legs as much as his knees. Nonetheless, he may really feel the new stones on his thighs and all over the place else on his physique. He additionally reported related tingling in his toes all the way down to his knees. He may transfer round with out issue and denied any latest trauma to his legs. He was residing at dwelling and never at the moment working. He doesn’t recall any publicity to heavy metals or industrial toxins prior to now. He was a present smoker and smoked half a pack a day and denied some other substance use. He had by no means been examined for HIV and was sexually energetic with two companions who used intermittent barrier contraception. His medical historical past contains Non-Small Cell Lung Most cancers (NSCLC) in post-chemoradiotherapy remission, continual prostatitis, prediabetes, nervousness, osteoarthritis, and melancholy. NSCLC was handled three years in the past, with a six month course of carboplatin-etoposide (each 4 weeks), and has been in remission for a 12 months now. His bodily examination revealed altered vibrational sensations bilaterally from the toes to each knees. He additionally had an altered sense of temperature overlaying the identical area. His gait was unremarkable and the remainder of his neurological, cardiac, pulmonary and gastrointestinal examinations had been benign.
An in depth workup was initiated, and his cell counts, blood chemistries, liver perform checks, HbA1c and sexually transmitted illness panel together with syphilis, gonorrhea, chlamydia, HIV and hepatitis , returned inside regular limits. Given a historical past of chemotherapy and an unremarkable preliminary workup, he was additionally evaluated for thiamine, pyridoxine, and cobalamin deficiency. As offered within the desk 1, his thiamine and cobalamin ranges had been regular and pyridoxine was at an abnormally low degree of 1.6 µg/L and was the one believable clarification for the affected person’s peripheral neuropathy, concurrently explaining the prognosis of melancholy. The affected person was positioned on oral replenishment with pyridoxine 100 mg as soon as day by day with enchancment famous inside three months of onset.
Utilizing a stepwise method to evaluate the reason for our affected person’s subacute/insidious acquired, symmetrical, distal, focal sensory neuropathy, a prognosis of remoted pyridoxine deficiency was established and managed.
Neuropathy, if left untreated, can result in irreversible axonal loss and everlasting deficits. Subsequently, identification of the right etiology is crucial for prevention of additional injury, in addition to potential reversal and administration of neuropathy. In contrast to crops and micro organism, mammalian cells can not synthesize pyridoxine, and dietary consumption with meat and greens in addition to manufacturing by intestine microflora are the supply of pyridoxine for people. . Dietary consumption of pyridoxine is 1-2 mg for adults and absorption is unsaturated . Pyridoxine, much like cyanocobalamin and folate, is important for the metabolism of methionine to cysteine and due to this fact mandatory for neuronal survival . Pyridoxine deficiency is understood to impair transcellular signaling between neurons and often presents because the end result of assorted non-specific signs which might be typically troublesome to place collectively. . Scientific indicators embrace melancholy, anemia, muscle convulsions, hyperirritability and peripheral neuropathy [3,5].
The causes of neuropathy could be labeled into two broad classes, inherited and purchased, the previous together with Charcot-Marie-Tooth (CMT) illness, hereditary transthyretin amyloidosis neuropathy, porphyria, Fabry illness, Refsum’s illness and metachromatic leukodystrophy. Acquired causes embrace medicine, toxins, immune-mediated, infectious, cancer-related, compressive, and metabolic ailments . Some drug-related causes of pyridoxine deficiency embrace isoniazid, penicillamine, levodopa, and chemotherapy medicine, which intrude with its metabolism.
The presence of peripheral neuropathy secondary to pyridoxine deficiency within the absence of sideroblastic anemia, much like our affected person, is a uncommon however recognized presentation of pyridoxine deficiency, which is reported within the literature however simply missed within the affected person evaluation. . Beforehand reported within the literature is a case report with remoted pyridoxine deficiency in a diabetic affected person, presenting solely as muscle spasms .
Carboplatin is a platinum-based chemotherapy drug used for the remedy of stable tumors, which bind to DNA nucleobases, resulting in replication and transcriptional suppression, apoptosis or necrosis of tumor cells. . Generally noticed adversarial results embrace myelosuppression, renal failure and peripheral neuropathy noticed in 4% to six% of sufferers after remedy. [8,9]. Spectroscopic research revealed the formation of a fancy between pyridoxine and carboplatin because of the structural similarity with adenine and guanine, leading to a lower within the most absorbance of pyridoxine in comparison with its baseline. . In an experimental examine on NSCLC, pyridoxine and pyridoxal kinase (PDXK) had been discovered to exacerbate, in a PDXK-dependent method, the cytotoxicity of cisplatin in vitro and in vivo. Expression of PDXK ranges capabilities as a prognostic biomarker for danger stratification in sufferers with NSCLC. Low ranges have been related to poor outcomes .
Pyridoxine in excessive doses interferes with the effectiveness of chemotherapeutic medicine and may precipitate neuropathy . Satisfactory administration of pyridoxine deficiency in sufferers in danger features a day by day dose of 6 mg of pyridoxine. A day by day dose better than 50 mg/day if used for greater than six months has been proven to be dangerous [4,12].
This case emphasizes the identification of pyridoxine deficiency as a uncommon however recognized reason behind peripheral neuropathy within the at-risk inhabitants and the monitored dosage of the vitamin attributable to its slim therapeutic index. Prophylactic vitamin B12 supplementation in sufferers present process chemotherapy is taken into account a cheap and protected possibility for stopping the event of cisplatin-induced peripheral neuropathy (CIPN). Nonetheless, this can be a tough state of affairs with pyridoxine supplementation as a result of, in excessive doses, it not solely interferes with the effectiveness of chemotherapeutic medicine however may also precipitate neuropathy; due to this fact, a pyridoxine take a look at is important earlier than prophylactic remedy. A robust suspicion of chemotherapy-induced peripheral neuropathy secondary to pyridoxine deficiency must be current even when the neuropathy presents late.