Australian Doctor 14th July Issue 14JULY2023 issue | Page 55

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SPOT DIAGNOSIS

TIM is a 28-year-old security shift worker who presents with a month of fatigue and bilateral leg pain . In the past week , he has developed a “ weird spotty ” rash on his legs and leg bruising , with no recollection of trauma . His leg hairs are also unusually curly ( pictured ). Tim is otherwise well , takes no medications and does not smoke or drink alcohol . He works long hours , saving for a home deposit , and often takes double or triple shifts . As a result , his diet is limited to what he can access and prepare at work — namely , coffee , toast , macaroni cheese , two-minute noodles and tinned tuna . His weight is stable , and he has had no associated fever or night sweats . He had pathology last week , which showed a microcytic anaemia with normal white cell and platelet counts , low ferritin and normal CRP , EUC and LFT .

On examination , the only significant findings are a generalised petechial rash , gingivitis and the lower-limb features pictured .

Conjugated bilirubin 50 77 < 8μmol / L ALP 267 261 35-110 U / L AST 125 136 10-40 U / L ALT 373 400 5-40 U / L GGT 512 337 5-50 U / L LDH 219 209 120-250 U / L

acute cholecystitis or choledocholithiasis . Liver biopsy indicates acute cholestatic hepatitis with no specific aetiological features . The pathologist suggests drug-induced liver injury ( DILI ), including that caused by herbal remedies , as the most common cause of this reaction pattern .

On further questioning , Ted admits to drinking three mugs of Aspalathus linearis ( rooibos ) daily .

The gastroenterologist advises , in addition to cessation of SSRIs , to avoid all herbal medicines .

Discussion

DILI may present in many forms , ranging from asymptomatic incidental findings of deranged liver biochemistry , to hepatocellular or cholestatic jaundice , liver failure , or chronic hepatitis . Antimicrobials , herbal and dietary supplements , and cancer therapies are the most common culprits in the Western world , but the range of potential causes is vast , and includes possible interactions between agents . 1

Herbal and dietary supplements account for a substantial and increasing proportion of cases globally . Around 20 % of US cases are due to such agents , 2 and in Australia , the proportion may be similar . 3 In the small Australian data set , bodybuilding and weight loss supplements , and traditional Chinese medicines were the most commonly reported , with cases also linked with kava , cassia , cinnamon and curcumin . 3

It can be difficult to identify rare or novel causes . The US National Institute of Diabetes and Digestive and Kidney Diseases and the US National Library of Medicine publish a searchable open access online resource ( LiverTox ) to aid clinicians to identify more enigmatic causes ( see online resource ). 1

Review of this resource reveals that liver

function abnormalities have been reported in up to 1 % of patients taking sertraline . Typically these are modest and do not require dose adjustment , however there are rare reports of acute liver injury with marked enzyme elevations and jaundice . 4

Rooibos is a herbal tea which is also known as bush tea , red tea or redbush tea . It is used in the same manner as black or green tea . It is generally deemed safe in terms of hepatotoxicity , but there may be a subset of drinkers who have a higher risk of liver injury . Due to effects on cytochrome P450 enzymes , there is also the potential risk of herb-drug interactions affecting bioavailability of some co-administered medicines . 5 At least one report of hepatotoxicity has been reported with high level consumption . 6 , 7

There have been no documented cases to date of liver dysfunction associated with resveratrol use identified on LiverTox .

Outcome

It is thought that the cause of DILI in Ted ’ s case is likely to be sertraline and concomitant rooibos consumption . He is advised to avoid all herbal medicines and SSRIs . He is commenced on nortriptyline 75mg nocte , which maintains his stable mental state . His LFTs normalise within three months and Ted remains well in himself .

Online resource :

LiverTox : Clinical and Research Information on Drug-Induced Liver Injury [ Internet ]. Bethesda ( MD ): National Institute of Diabetes and Digestive and Kidney Diseases ; 2012- . ncbi . nlm . nih . gov / books / NBK547852

References on request from kate . kelso @ adg . com . au

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ANSWER The answer is a . Unlike many other animals , humans cannot produce endogenous vitamin C via glucose metabolism . This water-soluble vitamin is vital for wound healing , immune function , neurotransmitter production , nitric oxide synthesis , osteoblast and fibroblast growth and to maintain the triple helical structure of collagen . Vitamin C also acts as a reducing agent for production of vitamin E , folic acid , iron and copper , which can lead to or compound the multiple vitamin deficiencies that are often seen in association with scurvy . 1

In the human diet , 90 % of vitamin C comes from citrus fruit and vegetables , such as sweet peppers , broccoli , cauliflower and tomatoes . Since the 1970s , the Western diet has changed dramatically , with increased availability and intake of potatoes , pizzas and carbonated drinks . In some groups , this has been associated with a reduced intake of fruits , vegetables and dairy products . Those at high risk for scurvy in the modern world include people who are prone to malnutrition via limited diet or restrictive eating ( eg , lower socioeconomic status , food insecurity , psychiatric illness , disordered eating , alcohol dependence ), those with limited food access ( eg , elderly living alone , homelessness ) or those with malabsorptive states ( eg , gastric bypass , coeliac disease ). 1-3 The estimated prevalence of vitamin C deficiency in the US is 7.1 %. 1 In Australia , ABS data from 2011 to 2012 found that fewer than 5 % of the population had inadequate intake of vitamin C , and an observational study involving medical inpatients at an urban tertiary hospital found that 76.5 % were vitamin C deficient . 2

Overt scurvy develops within 40-90 days of sustained hypovitaminosis C , but manifestations can appear within 30 days of dietary insufficiency . 1 Typical initial symptoms include weakness , arthralgias , myalgias and fatigue , especially in the upper legs and thighs . The subsequent stages may present with depression , follicular hyperkeratosis , poor wound healing , corkscrew hair and swollen gums . Later stages involve haemorrhagic features , like ecchymoses , perifollicular haemorrhage , petechiae , haemarthrosis and haemopericardium . 1 The diagnosis is confirmed by plasma or serum ascorbic acid level testing . 1-3 With appropriate treatment , constitutional symptoms may improve within 24 hours , skin manifestations within a few days and musculoskeletal symptoms within two weeks . 1

In this case , the patient has an undetectable vitamin C level of < 5 µ mol / L ( normal : 40 – 100 ). He was also deficient in vitamin B12 and folic acid , with normal coeliac serology . 2 These vitamin and mineral deficiencies corrected and all symptoms resolved within one month following supplementation with oral vitamin C 1g daily , elemental iron 210mg daily , folic acid 1mg daily and IM hydroxocobalamin . Dr Kate Kelso is a GP and medical editor at Australian Doctor . References on request from kate . kelso @ adg . com . au