Cocaine-induced Midline Destructive Lesions Research Articles

Limits of prosthetic rehabilitation of cocaine-induced midline destructive lesions: Time to change the paradigm

The steady rise in cocaine consumption, particularly in its snorted form, has led to the increased incidence of cocaine-induced midline destructive lesions (CIMDLs), a severe condition resulting from chronic cocaine use that leads to significant tissue destruction in the nasal and palatal regions. Four patients with CIMDLs are presented, all characterized by nasopalatine perforation. Each patient reported a spontaneous onset of tissue loss in the hard palate near the midline, with the affected area ranging from 2.3 to 5.1 cm². All patients had a history of psychiatric conditions, including depressive episodes but without other significant medical conditions, which contributed to an average delay of 9 months before seeking initial medical consultation. Treatment, which included the use of palatal obturators to improve quality of life, remains nonstandardized and, combined with the patients' continued cocaine use and refusal of addiction care, led to poor follow-up and persistent tissue damage. This clinical report underscores the need for a paradigm shift in managing CIMDLs, emphasizing the integration of addiction treatment and psychological support with prosthetic rehabilitation to optimize long-term outcomes and prevent relapse.

Cocaine-induced destruction of the palate: a diagnostic and management challenge

Cocaine usage is increasing at a rate faster than population growth worldwide. The habitual and chronic insufflation of pulverised cocaine is associated with the progressive destruction of the osseocartilaginous structures of the midface, termed cocaine-induced midline destructive lesions (CIMDLs). These entities present a challenging diagnostic picture, mimicking other infectious, malignant and inflammatory conditions associated with midface destruction. CIMDLs can present along a wide spectrum of disease, with minimal palatal perforation to extensive sinonasal destruction. With the increasing usage of cocaine, there is likely to be a concurrent increase in patients presenting to emergency departments with these destructive entities. Therefore, there is a need to create awareness of this uncommon entity and to document a systematic approach that must be adopted to reach a definitive diagnosis which will subsequently inform management. We report four clinical cases of CIMDLs at varying stages of the disease process which presented to the Dublin Dental University Hospital between January 2023 and June 2024 and document their multidisciplinary management from initial presentation to eventual treatment.

The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series.

In this multicentric study involving three London hospitals, we compared ANCA-positive and ANCA-negative cocaine-induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p-ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA-positive and ANCA-negative CIMDL patients or when comparing p-ANCA and c-ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p-ANCA pattern specifically targeting PR3 (p-ANCA, PR3 + MPO-). However, ANCA positivity or presence of a specific ANCA pattern wasnot associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine-induced ENT pseudo-GPA" instead of CIMDL. IV Laryngoscope, 134:2609-2616, 2024.

Cocaine-induced granulomatosis with polyangiitis-an under-recognized condition.

Cocaine and cocaine mixed with levamisole are increasingly used in the UK and result in significant direct nasal damage in addition to promoting vasculitis. Our aims were as follows: (1) to identify the main symptoms and presentation of cocaine-induced vasculitis; (2) to provide evidence regarding the best practice for the investigation and diagnosis of cocaine-induced vasculitis; and (3) to analyse the clinical outcomes of patients in order to understand the optimal management for the condition. We performed a retrospective case series analysis of patients presenting with cocaine-induced midline destructive lesions or vasculitis compatible with granulomatosis with polyangiitis (GPA) from two large tertiary vasculitis clinics between 2016 and 2021. Forty-two patients (29 Birmingham, 13 London) with cocaine-induced midline lesions or systemic disease were identified. The median age was 41 years (range 23-66 years). Current cocaine use was common, and 20 of 23 samples provided were positive when routine urine toxicology was performed; 9 patients who denied ever using cocaine were identified as using cocaine based on urine toxicology analysis, and 11 who stated they were ex-users still tested positive. There was a high incidence of septal perforation (75%) and oronasal fistula (15%). Systemic manifestations were less common (27%), and only one patient had acute kidney injury. Fifty-six per cent of our patients were PR3-ANCA positive, with none testing positive for MPO-ANCA. Symptom remission required cocaine discontinuation even when immunosuppression was administered. Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy. The ANCA pattern is not specific for cocaine-induced midline destructive lesions. Treatment should be focused on cocaine cessation and conservative management in the first instance in the absence of organ-threatening disease.

Cocaine-induced vasculitis and mimics of vasculitis

Cocaine is apsychotropic tropane alkaloid and stimulant drug. Nasal insufflation of cocaine powder is acommon route of administration. In Germany, cocaine is frequently adulterated with levamisole, an anthelminthic drug with immunomodulatory effects. Both substances are linked to various autoimmune conditions. Cocaine-induced midline destructive lesions cause aprogressive destruction of osteocartilaginous structures within the upper respiratory tract and can mimic localized granulomatosis with polyangiitis. In addition, systemic vasculitis due to cocaine and levamisole has been reported. Differentiation of these conditions from primary vasculitis can be challenging because antineutrophil cytoplasmic antibodies (ANCA) are commonly detected. Early diagnosis of these conditions is crucial as clinical improvement is closely related to drug cessation.

Gene Expression Analysis in Patients with Cocaine-Induced Midline Destructive Lesions.

Background and Objectives: Cocaine users may present with positive antineutrophil cytoplasmic antibodies (ANCA) and severe midline destructive lesions (CIMDL) which are histologically characterized by massive apoptosis. However, histopathological and laboratory studies suggest that autoimmunity may not be the main pathogenic driver. We analyzed gene expression both in cell lines of nasal mucosa exposed to cocaine and in CIMDL patients to determine whether genetic predisposition might cause such lesions, which are observed in a minority of cocaine abusers. Materials and Methods: The genetic expression profile of nasal mucosa exposed to cocaine was analyzed. Rare variants of expressed genes were searched in patients with CIMDL using exome sequencing and bio-informatics. Results: We identified 462 genes that were induced by cocaine, mainly related to apoptosis and autophagy in response to oxidative stress. Under the hypothesis that genes linked to the phenotype are also induced by cocaine itself, a rare variants burden test was performed to select genes that were significantly enriched in rare mutations. Next, 11 cocaine abusers with CIMDL and no other relevant medical comorbidities underwent exome sequencing, and 12 genes that were significantly enriched in the burden test and present in at least 10 patients were identified. An in-depth analysis of these genes revealed their involvement in apoptosis, tissue homeostasis, autophagy, and response to oxidative stress. Conclusions: Oxidative stress and rare genetic alterations in the response to reactive oxygen species, apoptosis, autophagy, and tissue regeneration are plausible drivers of damage affecting nasal mucosa exposed to cocaine crystals and, consequently, the pathogenic mechanism behind CIMDL.

AB0853 IGG4-RELATED DISEASE CAUSING OCULAR NERVE PALSIES AND ORBITAL APEX SYNDROME: CASE REPORT AND LITERATURE REVIEW

Background:IgG4-Related Disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory condition. The epidemiology is not well defined: it usually affects adults from middle-age onwards, predominantly male. Both B and T-cells are central in IgG4-RD pathogenesis, as demonstrated by the efficacy of B-cell depletion therapy.IgG4-RD can affect multiple organs including the central and peripheral nervous system, producing a constellation of clinical symptoms and signs, depending on the organ structures involved.IgG4-related orbital disease is relatively rare can implicate all extra-ocular muscles, structures emerging from the Orbital apex, optic canal, or superior and inferior orbital fissure. Depending on the structures involved, it can produce different or sometimes subtle clinical presentations, posing diagnostic challenge. There were case reports of IgG4-related ophthalmic disease misdiagnosed as intraocular tumour.Objectives:IgG4-RD is increasingly recognised as an entity affecting the head and neck region. However, it rarely involves skull base and presents with orbital apex syndrome. In this current case report, we describe an interesting case of IgG-related orbital disease presenting with ocular nerve palsies and orbital apex syndrome.Methods:Case report.Results:A 36-year-old gentleman with cocaine and alcohol misuse presented with a 2-month history of left sided headache, diplopia, recurrent ear infections, otalgia and hearing loss. Initial imaging suggested left otomastoiditis and intravenous antibiotics were commenced. Contralateral partial third nerve palsy with pupil sparing was elicited. 2 months later, there was worsening right eye ptosis, proptosis, right relative afferent pupillary defect, reduced visual acuity and colour vision as well as a near-complete ophthalmoplegia. Subsequent imaging showed worsening soft tissue swelling centred on the upper left parapharyngeal and masticator space, with multiple perineural enhancement and lateral extension to right orbital apex and orbital fissures. Blood tests only revealed raised IgG4 subclass. Infectious aetiology was excluded. Left nasal mass biopsy performed showed no fungal organism or malignancy. There were lymphoplasmacytic proliferation but no storiform fibrosis or obliterative phlebitis. IgG4 immunostaining on two assessable fields revealed 22 and 17 positive plasma cells respectively, and an IgG4: IgG ratio of <10%, and 50% in the other. Significant improvement was seen clinically and radiologically with antibiotics and a tapering regime of oral Prednisolone. Patient was commenced on Azathioprine as long term immunosuppression.Conclusion:A high degree of clinical suspicion is necessary to diagnose IgG4-RD when presenting with orbital apex syndrome and ocular nerve palsies,IgG4-RD can mimic mastoiditis of infectious aetiology. Other differentials may include cocaine-induced midline destructive lesions and granulomatosis with polyangiitis. The diagnosis can be supported by elevated serum IgG, elevated IgG index and pathognomonic histopathological findings. . The diagnosis of IgG4-related orbital disease should be deliberated on by a multidisciplinary group, with every effort being made to exclude an infectious aetiology, before embarking on immunosuppressive therapy.Primary treatment is with steroids. However, immunotherapy using azathioprine can be utilised in recurrent disease or patients with steroid intolerance.

COCAINE-INDUCED MIDLINE DESTRUCTIVE LESION WITH NASAL AND ORAL INVOLVEMENT: A CASE REPORT

A 28-year-old homeless man presented with 1-year history of weight loss, nasal turbinate, oral mucosal inflammation, and septum necrosis. Physical examination revealed odynophagia, otalgia, high fever, and perforation of the hard palate involving extensive destruction of the soft palate and oropharynx. The patient confirmed regular cocaine use of at least 2 years. Laboratory testing showed leukocytosis, HIV and Venereal Disease Research Laboratory test nonreactive, and culture-tissue positive for fungus. Computed tomography of the oral cavity revealed expansive, infiltrative, heterogeneous, and irregular formation involving rhinopharynx and nasal fossa associated with the destruction of inferior and middle turbinates, nasal septum, and middle maxillary sinus wall. Histopathologic examination of the soft palate and pharynx indicated ulceration, extensive necrosis, and acute inflammatory infiltrate without atypia, granuloma, or vasculitis. Excluding the hypotheses of granulomatous inflammation and neoplasia, the cocaine-induced midline destructive lesions diagnosis was recognized. The patient was referred to an otorhinolaryngologist and buccomaxillofacial surgeon for management and follow-up. A 28-year-old homeless man presented with 1-year history of weight loss, nasal turbinate, oral mucosal inflammation, and septum necrosis. Physical examination revealed odynophagia, otalgia, high fever, and perforation of the hard palate involving extensive destruction of the soft palate and oropharynx. The patient confirmed regular cocaine use of at least 2 years. Laboratory testing showed leukocytosis, HIV and Venereal Disease Research Laboratory test nonreactive, and culture-tissue positive for fungus. Computed tomography of the oral cavity revealed expansive, infiltrative, heterogeneous, and irregular formation involving rhinopharynx and nasal fossa associated with the destruction of inferior and middle turbinates, nasal septum, and middle maxillary sinus wall. Histopathologic examination of the soft palate and pharynx indicated ulceration, extensive necrosis, and acute inflammatory infiltrate without atypia, granuloma, or vasculitis. Excluding the hypotheses of granulomatous inflammation and neoplasia, the cocaine-induced midline destructive lesions diagnosis was recognized. The patient was referred to an otorhinolaryngologist and buccomaxillofacial surgeon for management and follow-up.

Cocaïne et lésions destructrices centro-faciales : à propos d'un cas

IntroductionCocaine use is associated with multiple complications, some of which can mimic systemic diseases, especially Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitis. We report a case of Cocaine Induced Midline Destructive Lesions (CIMDL) for which a diagnosis of granulomatosis with polyangiitis (GPA) was discussed. Case reportA 42-year-old male, cocaine consumer, was admitted in our department for a centrofacial destructive process. He had no extra ear, nose and throat (ENT) involvement. ANCA were positive with a perinuclear fluorescence pattern and an anti-Proteinase 3 specificity. Regarding this unusual immunologic pattern and in the absence of histological argument for a GPA, a diagnosis of CIMDL was made. ConclusionCIMDL is a centrofacial destructive process due to intranasal cocaine use. It is frequently associated with the presence of p-ANCA with both anti-HNE and anti-PR3 specificity.

The disease of Sigmund Freud: oral cancer or cocaine-induced lesion?

Sigmund Freud, the father of modern psychoanalysis, suffered from what was considered to be a malignant tumour spreading from the back of his palate. He underwent numerous surgical interventions and radiation therapy over the course of 16years. Such a long survival casts a shadow of doubt on the diagnosis of oral cancer that was given to Freud. The book "Freud: Living and Dying", in which the personal physician of Freud described in detail his patient's fight with oral cancer, was reviewed. Current and past evidence, as well as epidemiological data, on oral cancer and cocaine-induced midline destructive lesions were also reviewed. Tobacco and cocaine are both responsible for oral lesions and Freud was a dedicated cigar smoker as well as a user and defender of cocaine. Freud's medical records indicate that the main cause of Freud's oral disease was excessive smoking. On the other hand, the diagnosis of oral cancer does not seem to be entirely consistent with the 16-year-long survival of Freud. Freud used cocaine regularly in the 1890s, as reported by his personal physician, and it is possible that he continued taking it beyond that time period without feeling the need to inform his doctor. It is possible that the lesion that progressively and very slowly eroded the splanchnocranial structures of Freud was not a bona-fide cancerous malignancy, but rather, the necrotizing effect of cocaine use that has been previously reported to be responsible for some massive facial destructive lesions.

Cocaine induced midline destructive lesions

Cocaine induced midline destructive lesions

Palate perforation differentiates cocaine-induced midline destructive lesions from granulomatosis with polyangiitis.

SUMMARYCocaine abuse occasionally causes extensive destruction of the osteocartilaginous structures of the nose, sinuses and palate, which mimics the clinical picture of other diseases associated with necrotising midfacial lesions. The differentiation of cocaine-induced midline destructive lesions (CIMDL) and limited granulomatosis with polyangiitis (GPA) may be difficult, particularly if patients do not readily admit substance abuse. We studied 10 patients with CIMDL and palate perforation referred to our Unit between 2002 and 2015. All cases underwent nasal endoscopy, sinus CT or MRI and ANCA test. In 8 patients, a nasal biopsy was performed. The PubMed database was searched to review all cases of palate perforation described in patients affected by CIMDL or GPA. All 10 cases presented with septal perforation and inferior turbinate destruction. We found hard palate perforation in 7 patients, soft palate perforation in 2 patients, and perforation of both in one patient. ANCA testing was negative in 8 patients and positive in 2, with C-ANCA and P-ANCA specificity, respectively. A review of the English literature identified palate perforation in 5 patients with GPA and in 73 patients with CIMDL. The presence of palate perforation in patients with MDL may represent a clinical marker that strongly favors CIMDL over GPA.

Vascularites induites par la cocaïne et/ou le lévamisole

Cocaine use is a multifaceted diagnostic pitfall in the field of systemic vasculitides. The fact that Cocaine-Induced Midline Destructive Lesions (CIMDL) can be associated with Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and mimic localized granulomatosis with polyangitis is known for decades. In these cases ANCA target Proteinase 3 (PR3) and Human Neutrophil Elastase. More recently, levamisole adulterated cocaine has been implicated in a peculiar clinico-biological syndrome combining cutaneous vasculopathy and sometimes glomerulonephritis, and ANCA positivity with frequent double positivity (PR3 and myeloperoxydase). Clinician should be aware of the clinical and immunological hints to these diagnoses. The pathogenesis of such drug-induced auto-immune syndromes is poorly understood. Its studying may shed new light on the potential mechanism involved in tolerance breakdown in conventional ANCA-associated vasculitides.

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers

Objective: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.Methods: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio.Results: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD.Conclusions: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.

Multiple mucocutaneous ulcers associated with cocaine-induced midline destructive lesions

Cocaine-induced midline destructive lesions (CIMDL) occur in a small subset of cocaine users, who clinically present with inflammation and necrosis of facial midline structures such as the palate, nasal septum, turbinates, and sinuses. We present a patient with CIMDL occurring concomitantly with ulcers on the cheek and upper trunk. Multiple biopsy specimens from the cutaneous and mucosal lesions consistently showed a dense dermal/submucosal infiltrate of neutrophils and plasma cells, without vasculitis or thrombosis. The ulcers resolved following cessation of cocaine use.

Cocaine induced midline destructive lesions.

Review of the literature concerning cocaine induced midline destructive lesions (CIMDL). We reviewed the English literature regarding CIMDL involving the nose and its surrounding structures. The review is based on a search of the US National Library of Medicine (PubMed) online database from January 1st, 1982 to March 31st, 2013. CIMDL is a pathology that mimics systemic diseases with positive anti-neutrophil cytoplasmic antibodies (ANCA). The prevalence of CIMDL is considered to be about 4.8% among cocaine users. Clinical manifestations include hyposmia, facial pain, crusting, ulcers, nasal septal perforation, palatal perforation, sinus wall destruction, orbital erosion and damage of the anterior skull base. The presence of ANCA directed against human neutrophil elastase (HNE) is the most distinguishing feature of CIMDL. Toxicological tests, indirect immunofluorescence microscopy, antigen specific solid assay testing, histopathological analysis, apoptosis assay and MRI imaging concur in the clinical identification of CIMDL. The pathogenesis of CIMDL is poorly understood and implicates inflammatory, infective, proapoptotic and autoimmune mechanisms. CIMDL must be readily recognized by clinicians to provide appropriate treatment. Immunosuppressive therapy has no role in the treatment of CIMDL. Only abstinence can interrupt the progression of the disease.

Comprehensive Surgical Management of Cocaine-Induced Midline Destructive Lesions

This article presents a review of the literature and proposes a protocol for managing acute and chronic midfacial cocaine-induced injuries. This report describes a series of 4 patients affected by cocaine-induced midline destructive lesions. Three patients came to the authors' attention after 18 months of drug withdrawal and underwent surgical treatments to restore nasal and palatal morphology and function, and the fourth patient was referred because of acute cocaine-induced destructive lesions and was treated by aggressive debridement. An 18-month drug-free period is planned before beginning any reconstructive procedures in this latter patient. Long-term follow-up showed stable results without relapse of palatal fistulas and good esthetic nasal appearance in all 3 patients undergoing reconstruction. The fourth patient did not show any disease progression and will be monitored for drug withdrawal. Chronic cocaine consumption may cause multiple types of damage to the soft and hard tissues of the midface. Acute lesions must be addressed with aggressive debridement. As a result of chronic injury, the palate and nose are deformed in a very complex way and the vascularity of the remaining local tissues may be compromised or inadequate for flap harvesting. Palatal and nasal reconstructions are very delicate operations and should be addressed separately to maximize the predictability of the result.

Cocaine induced midline destructive lesions

Review of the literature concerning cocaine induced midline destructive lesions (CIMDL). We reviewed the English literature regarding CIMDL involving the nose and its surrounding structures. The review is based on a search of the US National Library of Medicine (PubMed) online database from January 1st, 1982 to March 31st, 2013. CIMDL is a pathology that mimics systemic diseases with positive anti-neutrophil cytoplasmic antibodies (ANCA). The prevalence of CIMDL is considered to be about 4.8% among cocaine users. Clinical manifestations include hyposmia, facial pain, crusting, ulcers, nasal septal perforation, palatal perforation, sinus wall destruction, orbital erosion and damage of the anterior skull base. The presence of ANCA directed against human neutrophil elastase (HNE) is the most distinguishing feature of CIMDL. Toxicological tests, indirect immunofluorescence microscopy, antigen specific solid assay testing, histopathological analysis, apoptosis assay and MRI imaging concur in the clinical identification of CIMDL. The pathogenesis of CIMDL is poorly understood and implicates inflammatory, infective, proapoptotic and autoimmune mechanisms. CIMDL must be readily recognized by clinicians to provide appropriate treatment. Immunosuppressive therapy has no role in the treatment of CIMDL. Only abstinence can interrupt the progression of the disease.

Pyoderma gangrenosum and Wegener granulomatosis-like syndrome induced by cocaine

Cocaine abuse is associated with various skin and rheumatological diseases that mimic primary autoimmune diseases, including retiform purpura with involvement of the ears, cocaine-induced midline destructive lesions (CIMDL), and eruptive pyoderma gangrenosum (PG). Previous reports have suggested the use of perinuclear antineutrophil cytoplasmic antibodies (pANCA) with specificity against human neutrophil elastase (HNE) to differentiate these cocaine-induced diseases from primary autoimmune diseases. We describe a case of a 54-year-old woman with a history of cocaine abuse, who had PG lesions on her legs with accompanying CIMDL and lung lesions similar to those seen in Wegener granulomatosis. Detection of HNE-positive pANCA, and improvement or clinical recurrence after cessation or consumption of cocaine, respectively, were key to differentiating this presentation from primary autoimmune disease.

Stimulants and the Lung

Illicit stimulants, such as cocaine, amphetamine, and their derivatives (e.g., "ecstasy"), continue to exact heavy toll on health care in both developed and developing countries. The US Department of Health and Human Service reported over one million illicit drug-related emergency department visits in 2010, which was higher than any of the six previous years. Both inhaled and intravenous forms of these substances of abuse can result in a variety of acute and chronic injuries to practically every part of the respiratory tract, leading potentially to permanent morbidities as well as fatal consequences--including but not limited to nasal septum perforation, pulmonary hypertension, pneumothorax, pneumomediastinum, interstitial lung disease, alveolar hemorrhage, reactive airway disease, pulmonary edema, pulmonary granulomatosis, infections, foreign body aspiration, infections, bronchoconstriction, and thermal injuries. Stimulants are all rapidly absorbed substances that can also significantly alter the patient's systemic acid-base balance and central nervous system, thereby leading to further respiratory compromise. Mounting evidence in the past decade has demonstrated that adulterants coinhaled with these substances (e.g., levamisole) and the metabolites of these substances (e.g., cocaethylene) are associated with specific forms of systemic and respiratory complications as well. Recent studies have also demonstrated the effects of stimulants on autoimmune-mediated injuries of the respiratory tract, such as cocaine-induced midline destructive lesions. A persistent challenge to studies involving stimulant-associated respiratory toxidromes is the high prevalence of concomitant usage of various substances by drug abusers, including tobacco smoking. Now more than ever, health care providers must be familiar with the multitude of respiratory toxidromes as well as the diverse pathophysiology related to commonly abused stimulants to provide timely diagnosis and effective treatment.