Report

Oxford, UK
International
IJD
Blackwell
1365-4632
45 Publishing,
Publishing
Journal Ltd,
of
Ltd.
Dermatology
2004

Diagnostic clinical features of pentazocine-induced ulcers

Diagnostic
Hry
REPORT
et al. clinical features of pentazocine-induced ulcers

H. R. Y. Prasad, MD, Binod K. Khaitan, MD, M. Ramam, MD, Vinod K. Sharma, MD,
Ravinder K. Pandhi, MD, Saurabh Agarwal, MBBS, Anju Dhawan, MD, Raka Jain, PhD, FRSC,
and Manoj K. Singh, MD

From the Departments of Dermatology & Abstract

Venereology, Psychiatry and Pathology, All Background Pentazocine was introduced in 1967 as a non-narcotic, nonaddicting analgesic.
India Institute of Medical Sciences, New However, the abuse potential of this medication was soon recognized, and cutaneous and
Delhi, India
muscular complications of pentazocine abuse have been reported.
Correspondence Methods Demographic and clinical data on 10 patients with pentazocine-induced ulcers
Binod K. Khaitan, MD attending the Dermatology Outpatient Department of the All India Institute of Medical
Department of Dermatology & Venereology Sciences (AIIMS), New Delhi, India between November 2000 and October 2002 have
All India Institute of Medical Sciences been compiled.
New Delhi 110029
Results Ten patients with pentazocine-induced ulcers were seen at AIIMS between
India
E-mail: binodkhaitan@hotmail.com November 2000 and October 2002, six of whom were female. The average age of these
patients was 32 years. The duration of the complaints ranged from 10 days to 7 years
(average 17.5 months). Nine of the 10 patients had past history of painful medical
conditions for which they had received pentazocine injections. All the patients presented
with deep ulcers and sinuses over the accessible sites. The margins of these ulcers were
hyperpigmented and indurated. Six patients had scars along the superficial vein access sites.
Three patients had puffy-hand syndrome, while two had muscle contractures. No underlying
psychiatric disorders were found in any of these patients. Urine screening for pentazocine
was positive in two patients. Antinuclear antibody (ANA), antineutrophil cytoplasmic antibody
(ANCA) and antibody against DNA (antidsDNA) tests and screening for infections such as
human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)
were negative in all patients.
Conclusions Pentazocine abuse can be suspected from cutaneous findings, even when the
patient does not volunteer a history of self-medication. Recognition of the condition will prevent
misdirected investigations and treatment. The patient should be encouraged to seek treatment
for drug dependence.

Introduction Materials and Methods

Pentazocine was introduced in 1967 as a potent analgesic for
parenteral use. Initially it was hailed as a non-narcotic, non-
addicting analgesic. However, by 1969, the abuse potential
of pentazocine had been recognized,1 and subsequently reports
of pentazocine abuse started appearing in the literature.2,3
Cutaneous complications of parenteral pentazocine use/abuse
were first reported in 1971,4,5 and since then other reports
have described deep punched-out ulcers,68 woody induration
of skin, 6,7 puffy-hand syndrome, 9 fibrous myopathy, 1012
polymyositis13 and venous thrombosis.14
Misdiagnosis of pentazocine-induced complications is quite
common, and may lead to incorrect treatment and consequent
adverse effects. We describe 10 patients with pentazocine-
induced cutaneous ulcers, who were diagnosed in our depart-
910 ment based on clinical features and past history.
This study is a compilation of all the cases who presented with
features of cutaneous complications of pentazocine abuse to the
Dermatology Outpatient Department of the All India Institute of
Medical Sciences (AIIMS), New Delhi, India between November
2000 and October 2002. A detailed history, including demographic
data, past medical history and prior interventions for complaints,
was taken. Any history of iatrogenic administration of pentazocine
or other drugs with abuse potential was noted. Patients and their
immediate relatives were interviewed in detail to establish whether
abuse of medications was occurring and to discover the source of
such medications, if any. Cutaneous examination was conducted
and findings noted. Routine investigations such as complete blood
counts, erythrocyte sedimentation rate, liver and kidney function
tests and chest X-ray were carried out. A skin biopsy was taken
from the edge of the ulcer and subjected to histopathological

International Journal of Dermatology 2005, 44, 910 915 2004 The International Society of Dermatology
Prasad et al. Diagnostic clinical features of pentazocine-induced ulcers Report 911

examination. Screening for immunological disorders such as
vasculitis was performed by serological assessment of
antinuclear antibodies (ANAs), antineutrophil cytoplasmic
antibodies (ANCAs) and antibodies against DNA (antidsDNA).
Screening for blood-borne infections such as hepatitis B virus
(HBV), hepatitis C virus (HCV) and human immunodeficiency
virus (HIV) was carried out. Urine was screened for the
presence of opioids, benzodiazepines, dextropropoxyphene
and buprenorphine by thin layer chromatography (TLC).15
Establishing a case of drug abuse is difficult, particularly
when the history of self-medication is not forthcoming. The
diagnosis in these 10 cases was based on many factors derived
from history, clinical examination and investigations. These factors
were as follows.
1 History of pentazocine self-medication.
2 Positive urine screening for pentazocine.
3 Chance finding of ampoules with the patient by relatives or the
treating physician.
4 Clinical features:
(a) Ulcers/scars along sites of venous access or at sites of IM
injections;
(b) Deep punched-out ulcers with surrounding hyperpigmented
and indurated skin;
(c) Woody induration of skin;
(d) Fibrous myopathy;
(e) Puffy-hand syndrome.
5 Past history of chronic painful medical or surgical conditions for
which they were treated with pentazocine injections.
6 Information from coworkers about drug abuse.
7 Easy access to pentazocine (e.g. from profession).
The confirmation of the diagnosis was more conclusive when
more features were present in a patient.
Results
A total of 10 patients (four male and six female, age 2043
years) with pentazocine-induced ulcers were seen at our out-
patient department between November 2000 and October
2002. The demographic details and past histories of the patients
are shown in Table 1. The duration of the cutaneous complaints
ranged from 10 days to 7 years (average 17.5 months). Previ-
ous diagnoses included cutaneous tuberculosis, pyoderma
gangrenosum and vasculitis. Previous treatments for the cuta-
neous lesions included antitubercular treatment, systemic
corticosteroids, azathioprine, cyclophosphamide, cyclosporine
and oral and topical antibiotics.
Nine of the 10 patients had a history of a painful medical
condition for which they had sought treatment, and all had
received pentazocine injections [intramuscular (i.m.) or intra-
venous (i.v.)]. Following medical use of pentazocine, four
patients stated that they self-medicated with the drug while the
remainder denied any pentazocine abuse. However, pentazocine

Table 1 Demographic profile of the patients with pentazocine-induced ulcers

Prior intervention
Age/ Past Iatrogenic Self-
Case sex Occupation Duration Diagnosis Treatment history pentazocine medication

1 36 / F Housewife 7 years Vasculitis Corticosteroids Chest pain Yes (IM/IV) Denied

and immuno-
suppressives
2 31 / F Housewife 1.5 years Pyoderma ATT, prednisolone, Chronic backache, Yes (IM) Denied
gangrenosum, dexamethasone, abdominal pain,
cutaneous pulse therapy, appendicectomy,
tuberculosis debridement cholecystectomy,
and grafting right oophorectomy
3 20 / F Nurse 6 months Antibiotics Pain in legs Yes (IV) + (IV)
4 28 / F Nurse 3 months Antibiotics Denied
5 27 / M Truck driver 6 months Cutaneous Antibiotics Chronic pancreatitis, Yes (IM) Denied
tuberculosis secondary diabetes
6 35 / F Drug store 5 months Antibiotics Migraine, history Yes (IM) Denied
owner of depression?
7 28 / M Restaurateur 3 years Abdominal pain Yes (IM) + (IV/IM)
8 43 / M Insurance 1.5 years Penicillin Migraine Yes (IM) + (IM)
employee
9 38 /M Labourer 2.5 years Pyoderma Dexamethasone, Abdominal pain, Yes (IM) + (IV/IM)
gangrenosum pulse therapy history of
attempted suicide
10 32 / F Nurse 10 days Abdominal pain Yes (IV) Denied

ATT, anti-tubercular treatment; IV, intravenous; IM, intramuscular.

2004 The International Society of Dermatology International Journal of Dermatology 2005, 44, 910 915
912 Report Diagnostic clinical features of pentazocine-induced ulcers Prasad et al.

Table 2 Clinical and investigation findings

Case Clinical features Urine screening Investigations

1 Ulcers/sinuses on buttocks, thigh, forearms, arm, waist. Positive for Echocardiography normal
Woody induration of skin. Scars at venous access sites. pentazocine HPE vasculitis
Puffy-hand syndrome. Difficulty in venous access.
2 Deep punched-out ulcers on both legs with surrounding Positive for Mantoux 0 0
hyperpigmentation and induration. Scars at venous pentazocine HPE vasculitis
access sites. Puffy-hand syndrome. Difficulty in
venous access.
3 Ulcers over wrist, cubital fossa, ankles with hyper- Negative HPE epidermal necrosis and
pigmented margins. Scars at venous access sites. neutrophilic abscess.
Puncture mark with thrombophlebits on calf. Puffy- Dermal neutrophilic
hand syndrome. Difficulty in venous access. infiltrate
4 Ulcers with a necrotic floor and hyperpigmented Negative HPE epidermal necrosis.
margins on finger. Multiple scars in a linear fashion on Neutrophilic vasculitis
upper limbs at site of venous access. Difficulty in venous
access.
5 Small superficial ulcers on deltoid region. Binding down and ND HPE epidermal clefts.
induration of skin on both arms, flexion contractures of both Perivascular neutrophils and
elbows with atrophy of muscles. Scars on gluteal region. lymphocytes.
USG abdomen chronic
pancreatitis
6 Erythematous tender subcutaneous nodules on left forearm. Positive for HPE perivascular
Linearly arranged ulcers with surrounding induration on left buprenorphine neutrophils, eosinophils and
forearm and scars at venous access sites. lymphocytes
7 Ulcers with bluish margin and induration of calves and Negative HPE epidermal necrosis.
ankles. Atrophy of limb muscles with fixed extension Dermal mononuclear infiltrate
contractures of knees and elbows.
8 Punched-out ulcers with surrounding induration and Positive for HPE epidermal necrosis and
hyperpigmentation on arms, thigh, buttocks. Diffuse dextropropoxyphene clefts. Neutrophilic vasculitis and
woody induration of skin. Scars on buttocks. panniculitis
9 Ulcers on legs, feet, hands with hyperpigmented, ND HPE subcorneal split.
indurated margins. Scars along veins. Perivascular neutrophils and
plasma cells
10 Punched-out ulcers on both cubital fossae with swelling ND ND
induration, tenderness and increased temperature over
forearms. Puncture marks and thrombophlebitis on
cubital fossae. Difficulty in venous access

HPE, histopathological examination; USG, ultrasonogram; ND, not done.

ampoules were found with two patients, who denied self-use
of the drug, and thin layer chromatography showed pentazo-
cine in the urine of these patients. The source of the drug was
established in seven cases. The commonest source (four cases)
was a privately owned chemist shop. These shops were run
either by the patient or by an associate of the patient. Three
nurses obtained the drug from hospital stores.
All 10 patients presented to us with a history of ulceration
over the extremities and / or buttocks (Table 2). All the lesions
were present at easily accessible sites and in areas usually used
for i.m./ i.v. injections. The lesions started as clear fluid-filled
bullae or a nodule. These primary lesions would burst open,
discharging blood-stained or oily fluid, forming sinuses and
ulcers. Superficial nodules would form ulcers which continued
to increase in size and depth. The deeper nodules formed
sinuses which continued to discharge oily fluid. Necrotic
eschars present initially at the floor of these ulcers fell off, ex-
posing deeper tissue such as muscles (Fig. 1). The ulcers had
hyperpigmented margins and the surrounding area was indu-
rated to a variable extent. The ulcers and sinuses healed in 1
3 months, while new nodules and ulcers continued to appear.
In the early stages, the areas of self-injection became erythe-
matous, swollen and firm, with raised temperature and ten-
derness, resembling an area of cellulitis. These complaints
subsided over a period of time, giving way to induration of the
skin. In some patients, small (1 2 cm) ulcers were present at
sites of venous access such as the cubital fossa, the lateral bor-
ders of the wrists, and the dorsae of the hands and feet (Fig. 2).
These ulcers had healed, leaving behind small atrophic scars
with underlying induration. Six patients had small scars

International Journal of Dermatology 2005, 44, 910 915 2004 The International Society of Dermatology
Prasad et al.
Figure 1 Deep necrotic ulcers with eschars on both legs (case 2)
Figure 2 Ulcers along the sites of venous access (case 3)
distributed linearly on the extremities at sites of superficial
vein access which are routinely used for i.v. injections and
blood sampling. Three patients had nonpitting edema of the
hands and feet, which is also known as puffy-hand syndrome
2004 The International Society of Dermatology
Diagnostic clinical features of pentazocine-induced ulcers Report 913
Figure 3 Nonpitting edema of both hands, known as puffy-hand
syndrome (case 2)
(Fig. 3), usually seen in opioid addicts. In two patients, the
early cellulitis-like features had subsided with muscle atrophy
and contractures. One patient had flexion contractures at
the elbow joints, while another patient had extension con-
tracture at the elbow and knee joints, with severe restriction
of mobility.
There was difficulty in peripheral vein access in five patients
and femoral veins had to be used for blood sampling. In one
patient, a central line had to be established to administer an
antibiotic to treat the secondary infection in the ulcers.
Psychiatric evaluation was carried out in seven patients.
One patient had been treated in the past with benzodiazepines
for depression, but did not have any features of depression
when she presented to us. One patient had attempted suicide
in the past. No underlying psychiatric abnormality was found
in any of the patients. They were premorbidly well adjusted
and were handling their responsibilities adequately.
Investigations
Blood cell counts, erythrocyte sedimentation rate, and liver
and kidney function tests were within normal limits in all the
patients. Fasting and random blood sugar levels were elevated
in one patient. Radiographic examination of ulcer sites did
not reveal any bony involvement in any of the patients. Serol-
ogy for vasculitis (ANA, ANCA and antidsDNA) was nega-
tive in all the patients. Screening for infections (HBV, HCV
and HIV) was negative in all patients.
Skin biopsies were performed in nine patients, and we were
able to review biopsies from seven patients. One biopsy was
superficial and included the epidermis and part of the papil-
lary dermis, three were transected through the reticular
dermis and four included subcutaneous fat. The epidermal
changes included necrosis of portions of the epidermis in four
biopsies, parakeratosis in two, and acanthosis and ulceration
in one each. Four biopsies demonstrated splits at various levels
of the epidermis (intraepidermal in two biopsies, subcorneal
International Journal of Dermatology 2005, 44, 910 915
914 Report Diagnostic clinical features of pentazocine-induced ulcers
in one, and dermoepidermal junction and subcorneal in one).
The split contained fibrin and neutrophils in all biopsies.
There was superficial and deep perivascular inflammation in
all the biopsies. In four, there was also a significant infiltrate
in the interstitium. Neutrophils were present in significant
numbers in the infiltrate in six biopsies. Other infiltrating cells
included lymphocytes, histiocytes and plasma cells. Eosi-
nophils were prominent in one biopsy. Fibrinoid degenera-
tion of the vessel walls with extravasation of erythrocytes was
noted in two biopsies, with vasculitis extending into the sep-
tae of the panniculus in one. Marked dermal fibrosis with
increased thickness of the dermis was noted in four biopsies,
with thickened septae in the panniculus of two biopsies.
Subcutaneous fat was included in four of the seven biopsy
specimens, of which one had neutrophilic septal panniculitis,
one had thickened septae and the remaining two were nor-
mal. No granulomas or giant cells were seen in any biopsy.
No polarizable foreign material was demonstrated in any of
the seven biopsies.
Reports of two other biopsies were available. These biop-
sies were reported to have vasculitis with fibrinoid necrosis
of vessels, fibrin thrombi and erythrocyte extravasation. The
panniculus was reported to be normal in one and no comment
was made in the other. Unfortunately, biopsies from these
two patients could not be procured for review.
Specific investigations were performed in three patients; in
case 2, mantoux was negative; in case 1, echocardiography was
normal; in case 5, an ultrasound scan of the abdomen showed
a dilated bile duct with pancreatic calcification. Urine screening
for drug abuse was carried out in seven patients. Pentazocine
was present in urine samples of two patients. Dextropropoxy-
phene and buprenorphine were found in one patient each.
Follow-up
After the diagnosis was explained to the patients and psychi-
atric consultation advised, six patients were lost to follow-up.
Two patients are being followed up. Their ulcers have healed,
Table 3 Diagnostic pointers for pentazocine-induced cutaneous ulcers
No. Diagnostic pointer
1 Irregular-shaped deep ulcers with black eschars and surrounding induration
2 Halo of hyperpigmentation
3 Ulcers / nodules / scars / along superficial veins
4 Woody induration
5 Needle pricks/thrombophlebitis
6 Puffy-hand syndrome
7 Difficulty in venous access
8 Fibrous myopathy
9 Apparent indifference of the patient (lack of discomfort)
10 Past history of a chronic painful medical condition
11 Prior iatrogenic administration of pentazocine
12 Patients associated with medical profession (relatively easy access to the drugs)
International Journal of Dermatology 2005, 44, 910 915
Prasad et al.
but the induration and muscle contractures persist. Case
1 refused psychiatric evaluation and left the hospital against
medical advice. She sought treatment at another institution,
where she died due to septic shock. Case 2 was treated with
naltrexone 50 mg orally for 6 months. Within this period all
her ulcers healed with indurated scars. A month after stop-
ping naltrexone, the patient came back with new nodules and
ulcers and her urine tested positive for pentazocine. She was
later lost to follow-up.
Discussion
The diagnosis of pentazocine-induced ulcers is suggested
by certain clinical findings. These diagnostic pointers are
presented in Table 3.
Two findings, which we find of particular diagnostic value,
are difficulty in gaining access to peripheral veins and puffy-
hand syndrome. The superficial veins could not be accessed in
five of our patients; this problem was found in patients who
administer the drug intravenously. Three of these patients
also had scars and/or ulcers along the veins. Repeated injec-
tions probably lead to sclerosis of the veins. A previous report
describes the occlusion of the deep venous system in pentazocine
abuse,16 but there are no descriptions of changes in superficial
veins.
Puffy-hand syndrome, i.e. nonpitting edema of the dorsae
of the hands sparing the fingers, can occur as a result of any
injectable opioid abuse.9 This syndrome was present in three
of our patients. Similar symptoms can also occur on the feet.
Puffy-hand syndrome was present in patients who had evidence
of intravenous pentazocine abuse, but not in those using other
routes. Occlusion of venous or lymphatic drainage, or both,
may be the cause of edema.
Reports in the literature have described patients who come
forward with a history of pentazocine self-injections and then
develop lesions.46 In such situations the diagnosis is obvious.
Most patients presenting to dermatologists deny drug abuse
Reference no.
4 8, 18
5, 7
Present report
48
14
9
Present report
1012
5
3 5, 7, 8
3 5, 8
3, 7
2004 The International Society of Dermatology
Prasad et al.
and refuse to accept this diagnosis. Investigations to establish
the presence of pentazocine in urine are very useful in making
the diagnosis, but their limited availability is a disadvantage.
Pentazocine can be detected in the urine by thin layer chroma-
tography, which is a qualitative test. Quantitative tests such
as gas chromatography and gas chromatography / mass spec-
trometry are available in the research setting.17 However, a
negative result does not exclude the diagnosis of pentazocine
abuse because urine screening tests detect the recent use of
pentazocine. If a patient has not used the drug in the 2 days
prior to the test, a negative result may be obtained.
It has been stated that pentazocine-induced ulcers tend not
to heal well with conservative treatment and that wide three-
dimensional excision followed by skin grafting is necessary.18
Our experience has been different. Three of our patients, who
were followed up for sufficient periods of time, showed spon-
taneous healing of ulcers with conservative treatment such as
local cleaning, and topical and systemic antibiotics for
prevention of infections.
The fear of social stigma, of alienation by family members
and of losing their jobs in people who are employed in the
health services leads many patients to deny pentazocine
abuse. They refuse psychiatric assistance and prefer to leave
the hospital and are lost to follow-up once a diagnosis of pen-
tazocine abuse is made. Six of our patients were thus lost to
follow-up. One patient sought treatment at another hospital
where she continued to receive corticosteroids and immuno-
suppressives on account of an initial diagnosis of vasculitis;
she died due to septic shock. Two patients continue to be
followed up by us regularly.
Conclusion
More attention needs to be focused on pentazocine-induced
ulcers, as awareness of this condition is limited. Certain diag-
nostic pointers help to establish the diagnosis clinically and to
prevent wrong diagnoses and consequent use of expensive
and unwarranted therapy. Definitive evidence of pentazocine
abuse, i.e. a history and its presence in the urine, may not be
present in all cases. In such a scenario, the clinical features are
of great importance.
References
1 Council on Drugs; American Medical Association. The
misuse of pentazocine: its dependence producing potential.
J Am Med Assoc 1969; 209: 1518 1519.
2004 The International Society of Dermatology
Diagnostic clinical features of pentazocine-induced ulcers Report 915
2 Inciardi JA, Chambers CD. Patterns of pentazocine
abuse and addiction. N Y State J Med 1971; 71:
1727 1733.
3 Swanson DW, Weddige RL, Morse RM. Hospitalized
pentazocine abusers. Mayo Clin Proc 1973; 48:
85 93.
4 Schlicher JE, Zuehlke RL, Lynch PJ. Local changes at
site of pentazocine injection. Arch Dermatol 1971; 104:
90 91.
5 Parks DL, Perry HO, Muller SA. Cutaneous complications
of pentazocine injections. Arch Dermatol 1971;
104: 231 235.
6 Schiff BL, Kern AB. Unusual cutaneous manifestations
of pentazocine addiction. J Am Med Assoc 1977; 238:
1542 1543.
7 Palestine RF, Millns JL, Spigel GT, et al. Skin manifestations
of pentazocine abuse. J Am Acad Dermatol 1980; 2:
47 55.
8 Mann RJ, Gostelow BE, Meacock DJ, et al. Pentazocine
ulcers. J R Soc Med 1982; 75: 903 905.
9 Neviaser RJ, Butterfield W, Wieche DR. The puffy hand of
drug addiction: a study of pathogenesis. J Bone Joint Surg
Am 1972; 54: 629 633.
10 Joong S, Rollins JL, Lewis I. Pentazocine induced fibrous
myopathy. J Am Med Assoc 1975; 231: 271 273.
11 Johnson KR, Hsueh WA, Glusman SM, et al. Fibrous
myopathy. A rheumatic complication of drug abuse.
Arthritis Rheum 1976; 19: 923 926.
12 Jain A, Bhattacharya SN, Singal A, et al. Pentazocine
induced widespread cutaneous and myo-fibrosis. J Dermatol
1999; 26: 368 370.
13 Kim HA, Song YW. Polymyositis developing after
prolonged injections of pentazocine. J Rheumatol 1996; 23:
1644 1646.
14 Girolami A, Cella G. Acute superficial phlebitis in a patient
with hemophilia A: probably a iatrogenic effect. Acta
Haemat 1972; 48: 307 311.
15 Jain R. Analytical methods. In: Jain R, ed. Detection of
Drugs of Abuse in Body Fluids. A Manual for Laboratory
Personnel. New Delhi: Drug Dependence Treatment Centre
AIIMS, 1998; 18 44.
16 Padilla RS, Becker LE, Hoffman H, et al. Cutaneous and
venous complications of pentazocine abuse. Arch Dermatol
1979; 115: 975 977.
17 Vereby K. Diagnostic laboratory: screening for drug abuse.
In: Lowinson JH, Ruiz P, Millman RB, eds. Substance
Abuse. A Comprehensive Textbook. Baltimore: Williams
and Wilkins, 1992; 425 436.
18 Cosman B, Feliciano WC, Wolff M. Pentazocine ulcers.
Plast Reconstr Surg 1977; 59: 255 259.
International Journal of Dermatology 2005, 44, 910 915