Split-thickness Skin Grafting in the Management of Cutaneous Sequelae of Intramuscular Pentazocine Injections: A Novel Approach

Pentazocine is a synthetic opioid that acts as a partial agonist at the kappa-opioid receptor and as an antagonist at the mu-opioid receptor. The drug was approved for use in the United States in 1967 for the treatment of mild to moderate pain, and it was marketed as a nonaddictive, nonnarcotic pain medication.¹ In the 1970s, recreational drug users discovered that combining pentazocine with certain antihistamines produced a euphoric effect. The drug was reclassified as a controlled substance, and newer formulations were prepared in combination with naloxone to prevent misuse.²

Not long after the introduction of pentazocine, dermatologic side effects at pentazocine injection sites were reported. These dermatologic manifestations included ulceration, panniculitis, so-called woody nodules, thrombophlebitis, and fibrous papules.¹ The most commonly described clinical features are also the most distinctive: expansive woody fibrosis extending beyond the injection sites, irregularly shaped deep ulcers that may extend into muscle, and halos of hyperpigmentation around the ulcers.³ Histologic analysis of the lesions often shows chronic panniculitis, thickened and fibrotic dermis, and inflammatory cell infiltration with eosinophils, histiocytes, polymorphonuclear leukocytes, and giant cells, with no evidence of foreign bodies.⁴

A 78-year-old male presented for surgical evaluation of a nonhealing ulcer on the right thigh. He had experienced a fall 3 years prior in which he sustained an abrasion to the thigh that did not heal. Diffuse woody sclerosis of the bilateral thighs and buttocks, with so-called leathery skin overlying these scleroses, were noted on physical examination. The patient explained that he developed this unusual chronic skin condition as a complication of intramuscular pentazocine injections decades before. According to the patient, he was diagnosed with ulcerative colitis in the late 1960s and suffered from severe uncontrolled pain. In the early 1970s, he was started on 3-times-daily intramuscular pentazocine injections. The patient injected himself in the proximal thighs and buttocks for a period of approximately 10 years. He gradually developed severe soft tissue calcifications of both buttocks and anterior thighs. In the mid-to-late 1980s, the patient underwent a complete colectomy with ileostomy, which resolved the pain from ulcerative colitis. Although pentazocine injections were discontinued at that time, the diffuse sclerosis and disfiguring fibrosis remained.

Despite the unusual appearance and texture of the patient’s skin, it was otherwise asymptomatic, and the patient was unbothered by it. However, 3 years before presenting to the authors of the current report, the patient sustained a fall with a superficial injury to the anterior right thigh. He subsequently developed several chronic soft tissue abscesses with draining purulent sinus tracts (Figures 1, 2). The patient underwent multiple rounds of surgical drainage, as well as twice-weekly wound care visits during which the wound beds were debrided and an NPWT device was placed. Secondary to the diffuse calcification and poor vascular supply resulting from the pentazocine injections, the wound healing capability of the skin was quite poor. Additionally, the wound matrix was poor and not ideal. The high calcium content of the wound resulting from chronic infection was difficult to remove. Use of V.A.C. Veraflo (3M) was not appropriate for this patient because the wound had calcified, and debridement was required to remove the calcification. After 2 years of unsuccessful attempts to obtain wound closure, the patient was evaluated by the surgical team. He then underwent 2 rounds of extensive excisional debridement of the skin and subcutaneous tissue of nearly the entire right anterior thigh, followed by STSG.

At the time of initial debridement, a hydrosurgery system (Versajet, Smith + Nephew) was used to establish a smooth wound bed. The extensive calcific spikes present throughout the wound were removed with rongeurs. Initial wound culture and subsequent cultures showed growth of Proteus mirabilis. After initial debridement the wound measured 28 cm × 15 cm × 2 cm, extending down to muscle (Figure 3). The patient was discharged with an NPWT device to a rehabilitation facility and then to his home with home health care.

At the 2-week follow-up, the patient reported significant drainage from the NPWT device. The patient then developed a wound infection, which required placement of a peripherally inserted central catheter line for IV infusions of amikacin and meropenem. Although the patient had medical insurance, he reported that the monthly cost of the IV antibiotics was quickly becoming a significant financial burden.

After 3 months of close follow-up with the surgical team and thrice-weekly wound care visits, the patient underwent another round of excisional debridement. A hydrosurgery system was used to excise the wound base down to healthy bleeding tissue, and a rotary tool with a cutting wheel was used to excise the calcific spikes more thoroughly in the wound base. Because of significant underlying dystrophic calcification in the left thigh as well, the skin was harvested carefully to avoid aggravating or inciting injury to that anatomic area. The skin graft was secured to the recipient site (total graft area, 297 cm²) (Figure 4). NPWT was placed, and the patient was discharged from the hospital 6 days later with topical mupirocin ointment. The patient followed up in the clinic every 2 weeks for the next 3 months, and the wound healed without complications (Figures 5–7).

The true incidence of sclerosis resulting from pentazocine injections is unknown and is believed to be underreported. In 1971, Parks et al³ described a patient with this complication, which was initially thought to be a rare outcome of pentazocine use; however, as additional patients presented with similar wounds, a strong link became evident.¹ Because of this, Parks et al³ suspected that many more cases of sclerosis have occurred but have been misattributed to other causes. In a different case series, the estimated incidence of skin fibrosis was seen in 3 in 1000 persons who misused pentazocine, although the true incidence is unknown.²

The hallmark findings of pentazocine-induced chronic ulcers are woody sclerosis of the skin and subcutaneous tissues around injection sites, halos of hyperpigmentation, and, interestingly, the seeming indifference of many patients to their disfiguring condition. It is likely that this noted indifference is responsible for an underreporting of this unusual but characteristic skin condition. The visual appearance of these pentazocine-induced skin lesions is so characteristic, in fact, that the diagnosis can often be made without further history-taking or diagnostic studies.^2,3 Although the pathophysiology of sclerosis is unknown, fibrosis and necrosis in the panniculus and muscles, possibly secondary to drug crystallization or its vaso-occlusive properties, have been noted in an animal model.^3,4

Management of the ulceration and sclerosis that occur secondary to pentazocine injections has not been well-documented in the literature. The literature focuses predominantly on the etiology of the wounds and their unique clinical presentation.^5-9 One study noted success with systemic and intralesional corticosteroids as well as aluminum hydroxide.¹⁰ In a more recent study, pamidronate infusions were used as a treatment method.¹¹ However, to the knowledge of the authors of the current case report, there are no reports in the literature of surgical management with skin grafting, and discussion of skin grafting as a potential treatment is sparse.

The case in the current report underscores the lasting effects of pentazocine-induced cutaneous sclerosis and fibrosis, with cutaneous complications occurring decades after use. It also highlights the novel use of STSG as a treatment strategy for these cutaneous complications.

Similar wound-related problems and difficulties can occur in patients with systemic sclerosis, who are also subject to calcium deposits in soft tissue. In these patients, nonsurgical options are explored initially, after which surgical options are pursued. There is no standard management or treatment for patients with scleroderma that has been successful.¹²

Although many patients may be asymptomatic or unbothered by the dermatologic side effects of pentazocine use, the patient in the current case report experienced complications that persisted for years. Whereas Magee et al¹⁰ documented successful management of smaller ulcers with steroids and aluminum hydroxide, the extent of the wound of the patient in the current case report demanded more aggressive intervention. In this case, the wound did not heal with NPWT or secondary intention; thus, STSG was deemed to be the best means to achieve definitive closure. Over the 3 months that followed, the graft matured well, and the wound fully healed without any further complications.

The current case is limited by the number of patients presenting with this rare manifestation of a discontinued drug. Although this case report is limited by a single patient and a discontinued drug, the management techniques used to treat this patient could be applied to similarly challenging wounds. Clinicians may confront similar circumstances with long-standing complications of similar medications. The patient in this case report presented with fibrosis and calcinosis resulting from use of pentazocine, and a wound management technique with STSG was used. Clinicians could apply this technique in other instances of calcinosis. Currently, there is no standard treatment for this type of wound; it is a rare finding that is difficult to manage. In addition, data on this type of wound and its management are sparse.

While there are many well-documented cases describing the development of fibrosis and calcinosis at the site of parenteral pentazocine injections, a review of the literature yields few reports documenting management or successful treatment of the long-term sequelae of these manifestations. Pentazocine-induced ulceration and panniculitis is an underrecognized, underdiagnosed, and underreported cause of chronic ulcers. Discussion of treatment of these ulcers is lacking in the literature.

This case report presents the successful treatment of chronic nonhealing ulcers with a novel use of STSG. Furthermore, this case shows that although pentazocine has not been widely prescribed in the United States for over 40 years, patients may experience complications of its use even today. Patients will experience the long-term effects of this drug for years to come. For this reason, it is important for physicians to be able to recognize these characteristic lesions and provide appropriate treatment for complications that may arise as a result of this unique condition.