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ORIGINAL ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 4  |  Page : 153-158

Limb ulcerations in patients who abuse pentazocine: A demographic and clinical study of an under-recognized etiology of hard-to-heal ulcers in Zaria, Northwest Nigeria


1 Division of Plastic Surgery, Ahmadu Bello University and Ahmadu Bello University, Teaching Hospital Zaria, Kaduna State, Nigeria
2 Department of Anesthesia, Ahmadu Bello University and Ahmadu Bello University, Teaching Hospital Zaria, Kaduna State, Nigeria
3 Department of Trauma and Orthopedic Surgery, Ahmadu Bello University and Ahmadu Bello University, Teaching Hospital Zaria, Kaduna State, Nigeria

Date of Submission22-Oct-2019
Date of Acceptance24-Oct-2019
Date of Web Publication10-Feb-2020

Correspondence Address:
Dr. Abdulrasheed Ibrahim
Division of Plastic Surgery, Ahmadu Bello University and Ahmadu Bello University, Teaching Hospital Zaria, Kaduna State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ais.ais_33_19

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  Abstract 


Background: Pentazocine-induced ulcerations are characterized by an indolent and intractable course. They constitute in their prolonged form a severely debilitating condition and require long-term multidisciplinary care. The purpose of this study was to analyze the sociodemographic and clinical profile of patients with pentazocine-induced ulcerations and highlight the unique set of challenges in their management.
Patients and Method: This is a retrospective study of the clinical records for all patients with pentazocine-induced ulcerations from June 2002 to November 2013. The diagnosis was established by a past history of pentazocine abuse and the finding of chronic nonhealing ulcers on physical examination. Study variables included clinical presentation and outcome. The outcome was classified as healing following ulcer excision and skin grafts, healing following debridement and dressings, amputation, and loss to follow-up.
Results: There were 8 males and 10 females with a mean age of 41 (range: 22–68 years). Employment in the health care profession was noted in eight patients: three were physicians and five were nurses. The time interval from the start of pentazocine injection to cutaneous changes ranged from 2 to 13 months. Ulcers were asymmetrical and deep with irregular shapes. The forearm and the thighs were the commonest locations of the ulcers. Split thickness skin graft after ulcer excision was done for two patients and skin grafts after repeated debridements in four patients. Two patients had above-elbow amputations and one patient had an above-the-knee amputation. Fifty percent (9 of 18 patients) refused surgical intervention and left the hospital against medical advice.
Conclusion: In this study, there was a preponderance of pentazocine-induced ulcerations among middle-aged, college-educated medical or paramedical professionals. The majority of the ulcers were large, deforming, and indolent. Ulcer excision and split-thickness skin graft as well as treatment for drug dependence and social support are mandatory for an optimal outcome.

Keywords: Chronic pain, chronic ulcerations, drug abuse, pentazocine


How to cite this article:
Ibrahim A, Abubakar ML, Yunus AA, Dahiru IL, Amaefulae KE, Asuku ME. Limb ulcerations in patients who abuse pentazocine: A demographic and clinical study of an under-recognized etiology of hard-to-heal ulcers in Zaria, Northwest Nigeria. Arch Int Surg 2018;8:153-8

How to cite this URL:
Ibrahim A, Abubakar ML, Yunus AA, Dahiru IL, Amaefulae KE, Asuku ME. Limb ulcerations in patients who abuse pentazocine: A demographic and clinical study of an under-recognized etiology of hard-to-heal ulcers in Zaria, Northwest Nigeria. Arch Int Surg [serial online] 2018 [cited 2020 Jun 6];8:153-8. Available from: http://www.archintsurg.org/text.asp?2018/8/4/153/278026




  Introduction Top


Five decades ago, pentazocine was introduced as a benzomorphan derivative of morphine with mixed agonist-antagonist actions toward opiate receptors.[1] It was described as a low-cost, parenteral analgesic drug.[2] It was also assumed that the non-opiate chemistry of pentazocine conferred a nonaddictive property with a wide margin of efficacy and safety.[1],[2] The recommended dose is 30 mg (intramuscular, subcutaneous, or intravenous route) which may be repeated every 3–4 hours, and the total daily dosage should not exceed 360 mg.[3],[4],[5]

Most patients are given pentazocine prescriptions for moderate to severe pain and subsequently continued self-injections despite apparent remission of the original clinical indication.[6] Euphoria is a major reason for repeated administrations and the motivation for continuing abuse is to avoid withdrawal effects.[4] Relapse is common and most abusers develop tolerance, tending to increase the dosage and frequency of the administration.[4],[6]

The ritual accompanying pentazocine injections often includes the use of unsterile supplies, the sharing of needles, and lack of skin antisepsis.[7],[8] Although the aim is to inject the drug intravenously, this is not always achieved. When the veins become less accessible, it is injected directly into the skin or muscle, which can lead to multiple cutaneous complications.[9],[10] The spectrum of presentation includes cellulitis, abscesses around the sites of injection, and multiple large, deeply penetrating chronic ulcers.[3],[8],[11],[12] These ulcers are characterized by an indolent, intractable course with the severe social and economic burden.[13] Although rarely contributing to mortality, they constitute in their prolonged form, a severely debilitating condition requiring long-term multidisciplinary care for successful healing.[12],[14]

Prescription drug abuse and dependence is a global social and health concern.[7] There are relatively few recent publications on parental pentazocine abuse and chronic non-healing ulcers, likely due to the decreased usage in developed countries.[10],[15] We have observed a surge in the incidence of non-healing ulcers following long-standing injections of pentazocine, and this may represent the tip of a drug abuse iceberg in Zaria, Nigeria. The purpose of this study was to analyze the sociodemographic and clinical profile of a patient cohort with pentazocine-induced ulcerations and highlight the unique set of challenges in their management.


  Patients and Method Top


We conducted a retrospective review of the clinical records for all patients with pentazocine-induced ulcerations treated at the Ahmadu Bello University Teaching Hospital Zaria, Kaduna state Nigeria from June 2002 to November 2013.

The diagnosis of pentazocine-induced ulceration was established by a history of pentazocine abuse for a chronic painful medical or surgical condition and, the finding of chronic non-healing ulcers on physical examination.[1],[6],[11] Exclusion criteria were patients with incomplete records. Data on sociodemographic factors were collected: age; gender; occupation; source of the drug; administration by self/other; and previous drug abuse. Other study variables included clinical presentation and outcome. The outcome was classified as healing following ulcer excision and skin grafts, healing following debridement and dressings, amputation, and loss to follow-up.


  Results Top


Twenty two patients presented with pentazocine-induced ulceration during the period under review and eighteen patients fulfilled the inclusion criteria, 4 patients had incomplete records. The sociodemographic details of the patients are shown in [Table 1]. There were 8 males and 10 females with a mean age of 41 (range: 22–68 years). Twelve of the eighteen patients had an equivalent of a bachelor's degree or a higher degree (university or college). Employment in the health care profession was noted in eight patients: three were physicians and five were nurses. Following the use of pentazocine, all the patients affirmed that they self-medicated with the drug. The source of the drug in 14 patients was over the counter in privately owned pharmacies or chemist shops and from the hospital pharmacy in four patients. None of the patients admitted to obtaining the drug by overprescribing or forgery. Two patients had a previous history of cannabis abuse.
Table 1: Sociodemographic characteristics of the patients with pentazocine-induced ulcerations

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An accurate estimation of total dosage was not obtained because the patients were defensive during history taking, especially about self-administration. The route of administration was established in all the patients. All had received intravenous, intramuscular, or subcutaneous injections of pentazocine. The administration was by self in 16 patients. The drug was administered either by the patient or other (case 13) [Table 1]. In one patient (case 12), it was exclusively by another person. The duration of administration ranged from 6 months to 5 years (average 28 months) [Table 1]. The time interval from the start of pentazocine injection to cutaneous changes ranged from 2 to 13 months. The duration of the ulcers ranged from 2 to 14 months. [Table 2]
Table 2: Clinical presentation and outcome

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Cutaneous findings consisted of multiple ulcerations, hyper-pigmented changes at the sites of pentazocine injections and diffuse induration [Figure 1]a and [Figure 1]b. Ulcers tended to be asymmetrical and deep with irregular shapes. The majority of the ulcers were 6–10 cm in diameter. The forearm and the thighs were the commonest locations of the ulcers [Table 2]. One patient had bilateral circumferential forearm ulcers with puffy hand syndrome [Figure 2]. Two patients had involvement of both lower limbs from the hips to the feet (Case 15 and 17).
Figure 1: (a) Multiple necrotic ulcerations on both thighs, (b) hyperpigmentation and woody induration of skin both forearms

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Figure 2: Bilateral circumferential ulcers of the forearms and non-pitting edema of the hands (puffy hand syndrome) (a) Right forearm and hand (b) Left forearm and han

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Split thickness skin graft after ulcer excision [Figure 3] was done for two patients and skin grafts after repeated debridements in four patients. Two patients had above-elbow amputations and one patient had an above-the-knee amputation. The indication for amputation in the three patients was florid necrotizing soft-tissue infection and osteomyelitis of the underlying bones. Not surprisingly, the majority of the patients were relatively noncompliant with the therapeutic recommendations. Fifty percent (9 of 18 patients) refused surgical intervention and left the hospital against medical advice.
Figure 3: (a) Pentazocine.induced ulcerations on both thighs, (b) excision of ulcers on both thighs, (c) satisfactory healing with split-thickness skin grafts

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  Discussion Top


The literature on pentazocine abuse is characterized by demographic trends that accord with age and occupation. The typical pentazocine abuser is described as middle-aged, university or college-educated, and associated with the medical or paramedical professions.[3],[6],[16] The results of this study are consistent with this sociodemographic profile. Ten patients were between the ages of 40 and 60. Twelve patients had university or college education, and their professions were reduced to four categories: physicians (three); nurses (five); lawyers (two); and armed forces/police (two). Glatt et al.[17] observed that four of the ten patients including three physicians abused pentazocine. Likewise, Palestine et al.[6] in their study reported that nine patients were in the medical or paramedical fields, and six of these were physicians. The number of abusers among medical and paramedical personnel is disturbing and has significant consequences for patient safety and public health[4],[18] Health care workers are generally considered to be at high risk for pentazocine abuse compared to the general population because of the easy access to the drug.[3],[6] Hospitals and professional organizations should develop programs to acknowledge the need for education about pentazocine abuse among health care professionals. Specifically, the information about the risks of prescription drug misuse including the problems associated with self-prescribing for medical conditions should be more strongly emphasized.[18]

In this study, pentazocine and cannabis abuse were reported in only two patients. This finding is similar to most of the available reports describing the abusers of pentazocine as solitary abusers.[6],[19] In contrast, the usual drug addicts are thought to use pentazocine rarely, and when they do use it, it is in the context of multiple drug abuse.[6] Kelly[20] reported that only three cases of pentazocine abuse were seen in more than 1000 drug addicts over a 3-year period. Regardless of the class of the drug abused in addition to pentazocine, almost all pentazocine being diverted for abuse can be attributed to the insufficient controls regulating its sale and distribution. The drug is commonly obtained by theft, forgery, overprescribing, and unregulated control of institutional drug supplies.[4],[19] There are only a few instances where pentazocine was offered for sale on the illicit drug market.[19] Diligence alone, in prescribing pentazocine will not prevent abuse. As with narcotic abuse, only strict statutory controls are likely to be effective and considerations should be given to enforcing the prescription of pentazocine as a controlled drug in our environment.[4],[15]

In this series, the reported commonest interval between repeated pentazocine injections and cutaneous changes was 6–12 months in 13 patients. This is comparable to the findings of previous studies.[6],[16] No single unifying hypothesis adequately explains the mechanism by which the injection of pentazocine induces cutaneous changes. Several authors have postulated that tissue precipitation of crystals from the intramuscular injection of pentazocine and trauma from repeated injections incites an inflammatory response.[3],[6],[7],[11] Pentazocine is acidic (pH 4.3) in nature and its crystals precipitate easily in a neutral or slightly alkaline medium.[7] This property, along with the trauma caused by repeated needling and rapid injections of large boluses of the drug, plays a significant role in the ensuing chronic inflammatory reaction.[7],[11]

In this study, two patterns of ulceration emerged depending on whether the patient administered the drug himself, or had it administered by someone else. The majority of the patients (16) reported self-administration and the commonest location of the ulcers were the thighs and the forearm. Only two patients reported administration by another, and the ulcers were located on the buttocks and the upper arm. This finding is consistent with the study by Irons et al.[21] They observed that ulcers from self- administered pentazocine were usually seen in parts of the body that were easily accessible to the patient; anterior aspects of the thighs and the forearm. They opined that self-administered injections were often into the dermis or fat which led to necrosis with subcutaneous thickening and fibrosis.[21] Palestine et al.[6] concurred and observed that progressive induration of the skin made injections more difficult. Areas too indurated for further injections subsequently softened and became reusable. This method of self-injection of pentazocine in any approachable soft-tissue, in desperation, when venous access dries up has been described as “blind dating” by Bhateja et al.[22] It is generally considered a trade-off between a deliberate attempt at intravenous “mainlining” and subcutaneous “skin-popping” injection patterns.[23]

The majority of the ulcers in this study were large, deforming, and asymmetric with varying shapes [Figure 1]a and [Figure 1]b. The evolution of a typical ulcer is initiated by a blanching at the site of the injection, which persists until it gradually evolves into a black eschar followed in the next several hours by the appearance of clear fluid-filled bulla or a nodule.[1],[16] These lesions would rupture spontaneously, discharging hemorrhagic fluid forming ulcers and sinuses.[24] Eschars present initially on the floor of these ulcers and fall off exposing deeper tissue such as muscle. The ulcers are indolent and very slow to heal.[1],[16] One of the patients in our series presented with circumferential ulcers and a “puffy hand” syndrome [Figure 2]. This is non-pitting edema of the hand following lymphatic obstruction caused by repeated injections.[24]

Parks et al.[1] observed that the diagnosis can be suspected even before a history of pentazocine injections is obtained. They outlined four distinctive clinical features that are invaluable, especially when patients deny the use of the drug. (i) a tense woody, expansive fibrosis that extends well beyond the sites of injection; (ii) irregularly shaped deep ulcers, some extending deeply to expose the underlying muscle; (iii) a halo of hyperpigmentation around the ulcers; and (iv) the apparent indifference of the patient toward the disfiguring process and their lack of expression of pain despite the degree of mutilation and tissue destruction.[3],[11],[16] It is important to differentiate pentazocine-induced ulcerations from other causes of chronic ulceration which appear similar. Lesions that should be considered in the differential diagnosis are vasculitis, pyoderma gangrenosum, venous insufficiency, cutaneous scleroderma, and toxic epidermal necrolysis.[11],[16]

A cardinal principle in the management is an immediate withdrawal of the drug as well as the treatment of the underlying cause of pain.[22] It is important to determine if the pain is acute and related to cellulitis/abscess or chronic pain from some other medical condition. Indeed, the treatment of pain can be extremely frustrating. Patients who have abused pentazocine have a decreased tolerance for pain. In addition, the patient's emotional response may also intensify the pain that is experienced. These patients will often require a combination of nonsteroidal anti-inflammatory drugs and an opioid in the setting of a multidisciplinary pain management team.[22],[23]

Concurrent psychiatric consultation to include appropriate psychological and social support is mandatory.[21] These patients will require the treatment for drug dependence by detoxification as well as psychoeducation and relapse prevention counseling.[22] In this study, only four patients had optimal psychiatric evaluation and management. This may reflect the fear of social stigma, of alienation by family members, and of losing their jobs, especially those employed in the health services.[24] Refusal of a psychiatric consultation will often lead to more difficult-to-treat patients with multiple, hard-to-heal ulcers.[9]

The treatment of the ulcers aims at effectively healing the lesions. A satisfactory outcome was seen in patients who had excision of the ulcers and skin grafts. [Figure 3] Several detailed reviews have demonstrated that proactive surgical management to include ulcer excision and split-thickness skin graft is the recommended standard procedure.[21],[25],[26] Areas of induration and fibrotic tissue at the injection site should be excised, usually down to bleeding muscle. Inadequate excision with epithelialized ulcers and unhealed tracts are likely to break down, leading to further ulceration.[25],[26] Extrapolating from the successful outcome with negative pressure wound therapy (NPWT) in preparation of the wound bed for skin graft in complex wounds, suggests significant advantages compared with conventional therapy.[27] It is invaluable in decreasing local edema, removing fluid and local debris, increasing peripheral wound perfusion and promoting granulation tissue formation. The duration of wound bed preparation is reduced and skin grafts on NPWT-treated wounds remain resilient and pliable several months after surgery.[27],[28] Some authors have concluded that this technology should be considered the treatment of choice for all hard-to-heal ulcers.[27]

A proportion of patients with pentazocine ulcers can be managed conservatively. Prasad et al.[24] reported spontaneous healing of ulcers with debridement and a combination of topical and systemic antibiotics. Mak et al.[16] also reported a successful outcome with conservative management in a frail patient with extensive ulceration. The wounds were dressed with hydrocolloid and foam dressings.[16]

Education is a critical component of prevention. Medical school and graduate paramedical curricula should explicitly cover topics pertaining to pentazocine abuse.[29] Furthermore, a supportive atmosphere in which individuals feel confident coming forward to disclose must be established in hospitals. This will aid in the early identification and intervention of pentazocine abuse among staff.[18] It will also provide a platform for support and counseling to recovered pentazocine abusers in their re-entry to safe professional practice.[18],[29]


  Conclusion Top


In this study, there was a preponderance of pentazocine-induced ulcerations among middle-aged, college-educated medical or paramedical professionals. The majority of the ulcers were large, deforming and indolent. Ulcer excision and split-thickness skin graft as well as treatment for drug dependence and social support is mandatory for an optimal outcome. Strict statutory controls to enforce the prescription of pentazocine and education are critical components of prevention in our environment. Hospitals and professional organizations should develop programs acknowledging a dire need for education about pentazocine abuse among health-care professionals.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Parks DL, Perry HO, Muller SA. Cutaneous complications of pentazocine injections. Arch Dermatol 1971;104:231-5.  Back to cited text no. 1
    
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Levy RM, Brown AR, Halikas JA. Illicit pentazocine (Talwin) use: A report of thirteen cases. Int J Addict 1972;7:693-700.  Back to cited text no. 2
    
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Furner BB. Parenteral pentazocine: Cutaneous complications revisited. J Am Acad Dermatol 1990;22:694-5.  Back to cited text no. 3
    
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King A, Betts TA. Abuse of pentazocine. Br Med J 1978;2:21.  Back to cited text no. 4
    
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Goldstein G. Pentazocine. Drug Alcohol Depend 1985;14:313-23.  Back to cited text no. 5
    
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Palestine RF, Millns JL, Spigel GT, Schroeter AL. Skin manifestations of pentazocine abuse. J Am Acad of Dermatol 1980;2:47-55.  Back to cited text no. 6
    
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Goyal V, Chawla JM, Balhara YP, Shukla G, Singh S, Behari M. Calcific myofibrosis due to pentazocine abuse: A case report. J Med Case Rep 2008;2:160.  Back to cited text no. 7
    
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Del Giudice P. Cutaneous complications of intravenous drug abuse. Br J Dermatol 2004;150:1-10.  Back to cited text no. 8
    
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Pirozzi K, Van JC, Pontious J, Meyr AJ. Demographic description of the presentation and treatment of lower extremity skin and soft tissue infections secondary to skin popping in intravenous drug abusers. J Foot Ankle Surg 2014;53:156-9.  Back to cited text no. 9
    
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Mudrick C, Isaacs J, Frankenhoff J. Case report: Injectable pentazocine abuse leading to necrotizing soft tissue infection and florid osteomyelitis. Hand (N Y) 2011;6:457-9.  Back to cited text no. 10
    
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Clemente Ruiz de Almiron A, Serrano Ortega S. Skin ulcerations due to pentazocine on both thighs. J Eur Acad Dermatol Venereol 2009;23:857-8.  Back to cited text no. 11
    
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Lloyd-Smith E, Wood E, Zhang R, Tyndall MW, Sheps S. Montaner JS, et al. Determinants of hospitalization for a cutaneous injection-related infection among injection drug users: A cohort study. BMC Public Health 2010;10:327.  Back to cited text no. 12
    
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Kathuria S, Ramesh V, Singh A. Pentazocine induced ulceration of the buttocks. Indian J Dermatol Venereol Leprol 2012;78:521.  Back to cited text no. 13
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Ebright JR, Pieper B. Skin and soft tissue infections in injection drug users. Infect Dis Clin North Am 2002;16:697-712.  Back to cited text no. 14
    
15.
Makanjuola AB, Olatunji P. Pentazocine abuse in sickle cell anaemia patients: A report of two case vignetes. Afr J Med Med Sci 2009;8:59-64.  Back to cited text no. 15
    
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Mak RK, Reynaert SM, O'Donoghue NB, Black MM. Atypical ulcerations. Clin Exp Dermatol 2006;31:311-2.  Back to cited text no. 16
    
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Glatt MM. A note on the misuse of pentazocine and dextropropoxyphene. Br J Addict Alcohol Other Drugs 1977;72:253-4.  Back to cited text no. 17
    
18.
Merlo LJ, Singhakant S, Cummings SM, Cottler LB. Reasons for misuse of prescription medication among physicians undergoing monitoring by a physician health program. J Addict Med 2013;7:349-53.  Back to cited text no. 18
    
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Chambers CD, Inciardi JA, Stephens RC. A critical review of pentazocine abuse. HSMHA Health Rep 1971;86:627-36.  Back to cited text no. 19
    
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Kelly MG, Pentazocine: A strong analgesic with low abuse potential. Br J Addict Alcohol Other Drugs 1977;72:250-2.  Back to cited text no. 20
    
21.
Irons GB Jr, Hodgkinson DJ, Chong GC, Woods JE. Pentazocine ulceration. Ann Plast Surg 1979;2:286-9.  Back to cited text no. 21
    
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Bhateja G, Subodh BN, Grover S, Basu D. Cutaneous complications with parenteral pentazocine dependence. German J Psychiatry 2006;9:53-6.  Back to cited text no. 22
    
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Pieper B, Hopper JA. Injection drug use and wound care. Nurs Clin North Am 2005;40:349-63.  Back to cited text no. 23
    
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Prasad HR, Khaitan BK, Ramam M, Sharma VK, Pandhi RK, Agarwal S, et al. Diagnostic clinical features of pentazocine induced ulcers. Int J Dermatol 2005;44:910-5.  Back to cited text no. 24
    
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Cosman A, Feliciano WC, Wolff M. Pentazocine ulcers. Plast Reconstr Surg 1977;59:255-9.  Back to cited text no. 25
    
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Warner RM, Srinivasan JR. Protean manifestations of intravenous drug use. Surgeon 2004;2:137-40.  Back to cited text no. 26
    
27.
Simman R, Phavixay L. Split-thickness skin grafts remain the gold standard for the closure of large acute and chronic wounds. J Am Col Certif Wound Spec 2011;3:55-9.  Back to cited text no. 27
    
28.
Werdin F, Tennenhaus M, Schaller HE, Rennekampff HO. Evidence-based management strategies for treatment of chronic wounds. Eplasty 2009;9:e19.  Back to cited text no. 28
    
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Bennett J, O'Donovan D. Substance misuse by doctors, nurses and other healthcare workers. Curr Opin Psychiatry 2001;14:195-9.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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