Alternative Remedies can cause harm if not regulated. Here's a case of rhabdomyolysis I presented several years ago due to a concoction of herbal tablets.

1. A case of Hepatotoxicity and
Myotoxicity associated with
an alternative remedy

2. Case History
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26 yr old female
Presented to A&E (15/10/2009) with 3 day history of
proximal myalgia of lower limbs, painful swollen
thighs and dark urine.
No complaints of myalgia remainder of body
Denied any systemic upset or infective symptoms
No history of trauma
Denied any drug misuse/overdose

3. Past Medical History

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March 09 - Campylobacter Gastroenteritis
Endometriosis
Asthma
Blackouts: no definitive diagnosis, attending
neurologist

4. Medications

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No regular medications
Trimethoprim (c/o by GP 24hrs prior to
admission)
Codeine phosphate 60mg PRN
Co-codamol 30/500 PRN
Non-smoker
Occassional alcohol

5. Examination
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Clinical observations stable
Afebrile
Heart sounds Normal
Chest clear on auscultation
Abdomen: mild RUQ tenderness, no
hepatomegaly
Upper limb examination unremarkable

6. 
Lower limbs:
Bilateral thigh swelling
 No erythema/ ↑temperature /crepitations
 Clinical proximal muscle weakness
 Calves SNT
 No ankle oedema

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Dipstick urine:
Protein ++
Blood +++
 -ve leucocytes/nitrates
 Microscopy: no casts


7. Initial Laboratory Investigations
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WCC: 5.81
CRP: 109.34 mg
CK: 149 000 IU/L↑↑
Troponin T: <0.01
Coagulation screen (N)
LDH:2286
Renal function:
Potassium 3.2 mmol/L
 Ur 2.1 mmol/L
 Creat:67 µmol/L
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Liver Enzymes
Bili: 5.3
 AST:2427
 ALT:670
 ALP:95
 GGT:67
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Phosphate 1.51 mmol/L
Corrected Calcium 2.06
mmol/L

8. Initial Diagnosis
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Inflammatory myositis of thigh muscles
Aetiology:
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?viral
?polymyositis
?drug induced

9. Management
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Aggressive IV fluid therapy initiated
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Post-take Ward Round
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Attended an alternative therapy practitioner in
Dublin 4/52 previously, prescribed combination of
tinctures and capsules
Ingestion discontinued on admission to hospital

10. Constituents of Alternative Remedy
Piper methysticum
(Kava)
Agaricus (field
mushroom)
Chinchona (Jesuit’s
Bark)
Ginseng
Lycopodium
(Clubmoss)
Staphisagria
(Delphinium)
Alfalfa
Guar Gum Capsules
Trace Elements (Co,
Mn, Cu)
Freeze dried bacteria

11. Units / L
Creatine Kinase levels during Miss S's admission
160000
140000
120000
100000
80000
60000
40000
20000
0
15/10/2009
16/10/2009
18/10//09
Date
19/10/2009
20/10/2009

12. AST and ALT levels during Miss S's admission
3000
Units / L
2500
2000
AST
ALT
1500
1000
500
0
09
09
09
09
09
09
09
09
/20
/20
/20
/20
/20
/20
/20
/20
0
0
0
0
0
0
0
0
5/1
7/1
8/1
1/1
6/1
9/1
0/1
2/1
1
1
1
1
1
2
2
2
Date

13. Clinical Course
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Daily improvement in myalgia
Repeat urine dipstick: Negative for further
haem pigment
No deterioration in measured renal function
Patient discharged home 4 days later
Biochemical normalisation of liver / muscle
enzymes by day 10 following discharge

14. Further Investiagtions
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Anti-CCP antibodies -ve
Autoantibody screen –ve
Complement levels within normal ranges
Rheumatoid factor –ve
Hepatitis screen –ve
CMV IgM –ve
Monospot test –ve
EBV IgM +ve

15. Discussion
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In the case of Miss S, it is postulated that
constituents of the herbal remedy were
responsible for provoking skeletal muscle and
hepatocellular injury, and resolved with
cessation of the medications.

16. The Extent of the Problem
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Herbalists ≠ Physicians
Regulation
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Evidence Base
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In UK, Traditional Herbal
Medicines Registration Scheme
(2005)
Variable potency of unlicensed
remedies
Cost-effectiveness?
Potential Harm
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MHRA guidelines
Legislation

17. Kava (Piper Methysticum)
Consumed throughout Pacific
Cultures as a beverage
Roots contain kavapyrones which
have anxiolytic properties
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Cochrane review recommended
potential for use in 2003
Less enthusiastic review 2006
Kavapyrones are also potent
inhibitors of cytochrome P450
system of the liver

18. Kava Hepatotoxicity
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Multiple Case Reports of varying degrees of hepatic
injury attributed to ingestion of kava.
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Idiosyncratic unpredictable reactions
Prohibition
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Medicines for Human Use (Kava-kava) (Prohibition)
Order 2002 (UK)
Germany / Switzerland
Under strict regulation
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National Code of Kava Management (Australia)
USA – FDA warnings and regulation

19. Council for International Organizations
of Medical Sciences (CIOMS) Scale
Type of liver injury
Hepatocellular
Points
Time of onset of the
event
First
exposure
Second
exposure
—
Time from drug
intake until reaction
onset
5 to 90 days
1 to 15 days
2
Time from drug
withdrawal until
reaction onset
<5 or >90
days
>15 days
1
≤15 days
≤15 days
1
Age ≥ 55 years
1
3
2
—
1
Lack of information or no
improvement
0
Worsening or <50%
improvement 30 days
-1
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1
>50% improvement 30 days
Course of the
reaction
Alcohol
>50% improvement 8 days
Risk factors
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Concomitant therapy:
Exclusion of nondrugrelated causes:
Previous information on
hepatotoxicity:
Response to readministration

20. Alternative Postulates
Miss S did not describe hallmark features of acute EBV
infection on admission.
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Did glandular fever prompt a visit to the practitioner 4
weeks previously?
EBV IgM can be detected in serum up to 6 weeks post
infection
In acute EBV infection Liver transaminases usually 2-3
X upper limit of normal (ULN)
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Levels >10 X ULN atypical and recommended an
alternative diagnosis be sought.
Rhabdomyolysis is a novel (but rare) complication of EBV
viraemia

21. Agaricus Extracts
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>300 species of the
fungal genus Agaricus
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Includes cultivated
button and common
field mushrooms

22. Mushroom Poisoning: Myotoxicity
Tricholoma equestre and
Russula spp.
 Patients reported fatigue and
muscle weakness
accompanied by myalgia,
mainly in the upper part of
the legs and dark urine
 Fatalities - myocarditis and
acute kidney injury

23. Mushroom Poisoning: Myotoxicity
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Experimental studies demonstrate the
reaction is not specific to these species
CK and AST levels increased with
other edible species of mushroom in
mouse studies
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No histological changes seen
Significant repeated doses of
mushroom required
Human equivalent doses
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Large but not unachievable

24. Conclusion
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This case highlights the serious and potential
fatal side-effects of herbal remedies prescribed
by alternative practitioners.
EBV viraemia may have prompted herbalist
attendance & potentiated the hepatitis.
Highlights the need to enquire about
complementary therapies.
CSM warnings

25. 
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References:
Bedry R, Baudrimont I, Deffieux G, Creppy EE, Pomies JP, Ragnaud JM,
Dupon M, Neau D, Gabinski C, De Witte S, Chapalain JC, Godeau P.
Wild-mushroom intoxication as a cause of rhabdomyolysis. NEJM
345:798–802, 2001.[
Crum NF. Epstein Barr Virus Hepatitis: Case Series and Review. Southern
Medical Journal: Vol 99,No 5, May 2006
Osamah H, Finkelstein R, Brook JG. Rhabdomyolysis complicating acute
Epstein-Barr virus infection. Infection 1995;23:119-120 Pittler MH, Ernst
E.
Kava extract versus placebo for treating anxiety. Cochrane Database of
Systematic Reviews 2006, Issue 1. Art. No.: CD003383. DOI:
10.1002/14651858.CD003383.
CIOMS scale from http://en.wikipedia.org/wiki/CIOMS/RUCAM_scale
Nieminen P, Kärjä V, Mustonen AM Myo- and hepatotoxic effects of
cultivated mushrooms in mice. Food Chem Toxicol. 2009 Jan;47(1):70-4.
Epub 2008 Oct 14.
Nieminen P et al. Suspected Myotoxicity of Edible Wild Mushrooms. Exp
Biol Med 231:221–228, 2006