Journal of Orthopaedic Surgery 2009;17(2):223-6

Necrotising fasciitis caused by adulterated

traditional Asian medicine: a case report
Hitendra K Doshi,1 Joseph Thambiah,1 Cheng Leng Chan,2 Min En Nga,3 Paul Ananth Tambyah4
1
Department of Orthopaedic Surgery, National University Hospital, Singapore
2
Center For Drug Administration, Health Sciences Authority, Singapore
3
Department of Pathology, National University Hospital, Singapore
4
Department of Infectious Diseases, National University Hospital, Singapore

‘chronic disease triad’—arthritis, musculoskeletal

ABSTRACT
Necrotising fasciitis can be life threatening, requiring
prompt diagnosis and surgical debridement. We
report a case of necrotising fasciitis caused by an
adulterate traditional Asian medication—Jamu Pegal
Linu, containing toxic levels of phenylbutazone
and dipyrone. The patient presented with severe
neutropenia and sepsis. An urgent extensive
debridement was carried out (within 6 hours of
presentation). Repeated debridements were performed
on days 2 and 5, augmented with antibiotics and
granulocyte colony-stimulating factor.
Key words: dipyrone; fasciitis, necrotizing; medicine,
traditional; neutropenia; phenylbutazone
disorders, and stroke.1 Acupuncture and moxibustion
may result in infection and necrotising fasciitis,2 as can
non-traumatic topical application of herbal products.3
It is important to be aware of the pharmacological
content of the medication, particularly when it is
systemically administered. Nonetheless, the contents
may remain uncertain owing to adulteration.
Jamu is a traditional Indonesian herb widely used
for centuries.4 Some Jamu medications have been
adulterated with phenylbutazone and diazepam,5
despite claims that they are made of natural herbs.
We report a patient who developed neutropenia
and necrotising fasciitis after consuming Jamu Pegal
Linu for a month. Pharmacological studies of the
medication detected the presence of phenylbutazone
and dipyrone.

CASE REPORT
INTRODUCTION
In February 2005, a 50-year-old Malay man presented
Traditional medicine is widely used in Asia for the with a 10-day history of a painful, swollen, and

Address correspondence and reprint requests to: Dr Hitenbra K Doshi, Department of Orthopaedic Surgery, National University
Hospital, 5 Lower Kent Ridge Road, Singapore 119074. E-mail: hitendra_doshi@yahoo.com
224 HK Doshi et al. Journal of Orthopaedic Surgery

Figure 1 A sample of Jamu Pegal Linu.

erythematous left leg. He had consumed traditional

medicine—Jamu Pegal Linu (Fig. 1)—as an aphrodisiac
and general stimulant for the previous month. No Figure 2 Localised skin necrosis with marginal surrounding
other medication was used. He developed fever and erythema over the thigh with extensive area of warmth and
rapid progression of the lesions in his thigh and calf. tenderness on day 1.
He had a blood pressure of 101/47 mm Hg, a heart
rate of 114 beats/minute, a temperature of 36.2ºC, a
respiratory rate of 26 breaths/minute and was alert Table
and oriented. His left leg had widespread violaceous Haematological and biochemical test results
discolouration, with early skin necrosis but no bullae Tests Results
(Fig. 2). Blood tests revealed pancytopenia, marked
Haemoglobin (g/dl) 8.7*
neutropenia, mild anaemia, and thrombocytopenia, Red blood cell (x1012/l) 2.88*
with a markedly elevated C-reactive protein (CRP) Total white cell (x109/l) 0.17*
and metabolic acidosis (Table). Polymorphs 0.01
The patient was resuscitated. Urgent magnetic Lymphocytes 0.14
resonance imaging (MRI) showed subcutaneous Monocytes 0.02
Eosinophils 0.00
oedema suggestive of cellulitis but was not diagnostic Basophils 0.00
for necrotising fasciitis (Fig. 3). After consultation Platelets (x109/l) 136*
with the infectious disease team, an urgent extensive Blood sugar (mmol/l) 27.2
debridement was carried out (within 6 hours of Urea (mmol/l) 13.9
presentation). Repeated debridements were performed Creatinine (mmol/l) 278
Sodium (mmol/l) 127
on days 2 and 5. Fascial and muscle biopsies revealed Potassium (mmol/l) 3.9
necrosis of the adipose tissue and fibrous septae in Erythrocyte sedimentation rate (mm/h) 131
addition to inflammation and thrombosis of the C-reactive protein (normal, <0.6) [mg/dl] 24.3*
subcutaneous vessels (Fig. 4). Blood and tissue cultures pH 7.36
were positive for Staphylococcus aureus sensitive pO2 (mm Hg) 81.8
pCO2 (mm Hg) 34.4
to oxacillin. Intravenous cloxacillin, clindamycin, Bicarbonate (mmol/l) 19.3
gentamycin, and subcutaneous granulocyte colony- Base excess (mmol/l) -5.4
stimulating factor were administered from days 2 to
10. On day 10, the wound granulated well (Fig. 5). A * Significantly abnormal
skin graft was placed over the left thigh and calf and
the patient was discharged on day 28.
The traditional medicine contained 25.2 mg/g of patient was followed up for 3 years.
dipyrone and 6.1 mg/g of phenylbutazone. The patient
thus consumed 176.4 mg of dipyrone and 42.7 mg of
phenylbutazone daily (2 packets a day weighing 7 g) DISCUSSION
for one month. A media alert was issued to identify
the source of, and halt the trade in, this product. The Phenylbutazone toxicity may involve the bone
Vol. 17 No. 2, August 2009 Necrotising fasciitis caused by adulterated traditional Asian medicine 225
Figure 3 Subcutaneous oedema in the left medial thigh
extending to the ankle. There is no abnormally high signal
in the intermuscular septa suggesting necrotising fasciitis or
oedema.
(a) (b)
(c)
Figure 4 (a) Fat necrosis
with a central infarcted
vessel (H&E, x20), (b)
fibrin thrombi and
adjacent necrotic fascia
(H&E, x200), and (c) an
infarcted vessel encrusted
with bacteria (H&E, x200)
marrow (agranulocytosis, aplastic anaemia), renal and
cardio­vascular systems (fluid retention to acute renal
failure), and have gastro-intestinal effects (dyspepsia
to perfo­rated ulcers). Other serious concerns include
hypersensitivity reactions, neurologic, dermatologic,
and hepatic toxicities. Agranulocytosis is a serious
and common adverse reaction. Dipyrone and
phenylbutazone are common causes of drug-induced
agranulocytosis or neutropenia.6 Chinese herbal
medications adulterated with phenylbutazone have
caused agranulocytosis.7
Neutropenia increases susceptibility to bacterial
infection leading to necrotising fasciitis. Some
Figure 5 The healthy soft-tissue bed of muscle on day 10
after multiple extensive debridements of skin, subcutaneous
tissue and muscle fascia.
paediatric oncology patients with chemotherapy-
induced neutropenia have developed necrotising
fasciitis and myonecrosis.8,9 It has been suggested
that non-steroidal anti-inflammatory drugs such as
phenylbutazone may be associated with necrotising
fasciitis,10 independent of agranulocytosis.
Granulocyte colony-stimulating factor was
administered to our patient as an adjunctive therapy
for the severe neutropenia because it achieves a
more rapid normalisation of the peripheral blood
granulocyte count and a reduced incidence of fatal
complications in patients with leukaemia.11 In non-
leukaemic patients with severe sepsis, its benefits
have been less clearly demonstrated.12
Necrotising fasciitis is categorised into type 1,
2 or 3, depending on the microbiology and clinical
presentation. People with underlying risk factors are
more likely to have type 1 necrotising fasciitis that is
polymicrobial or caused by Gram-positive organisms
other than group A streptococci,13 as did our patient.
Strong clinical suspicion is required for making a
diagnosis of necrotising fasciitis. Clinical, biochemical,
and radiological investigations may help establish
226 HK Doshi et al. Journal of Orthopaedic Surgery

the diagnosis. A raised white cell count is often seen
in necrotising fasciitis,14 but is unlikely in neutropenic
patients. A raised CRP level is an indicator of acute
inflammation and is significantly higher in patients
with necrotising fasciitis than those with cellulitis,15
and is even higher in neutropenic patients.
MRI findings are non-specific for necrotising
infection of the soft tissue.16 Our patient was
neutropenic and thus unable to mount a full
inflammatory response. A biopsy and frozen section
is useful for differentiating necrotising fasciitis from
severe cellulitis early on.17 Histological investigation
is the standard means of confirming the diagnosis.
Clinicians need to be alert to the possible adulteration
of traditional medications with toxic compounds.
ACKNOWLEDGEMENTS
We thank Ms Jamaliah from the Department of
Orthopaedic Surgery, National University Hospital
for assistance in formatting the article.

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