Cocaine-associated plasma cell orificial mucositis: Anything goes

By Warren R. Heymann, MD, FAAD, April 1, 2026

Vol. 8, No. 4

Sánchez-Puigdollers et al. have thoroughly reviewed cutaneous and mucosal disorders associated with cocaine use. Cocaine is an alkaloid obtained from the leaves of the Erythroxylum coca plant, acting as a central nervous system stimulant, a potent vasoconstrictor, and a local anesthetic. Cocaine is usually snorted or inhaled and is only uncommonly used intravenously. Ischemic and necrotic manifestations may be local (nasal mucosa erythema, ulcers), systemic (Raynaud phenomenon, distal ulcers, gangrene), and cause midline destructive lesions of the oronasal mucosa, perichondrium, and maxillary sinuses. Immune-mediated and neutrophilic conditions include the ANCA-associated vasculitis/cocaine-levamisole-associated autoimmune syndrome (presenting as ulcerative retiform purpura on the ears, nose, cheeks, fingers, toes, and trunk), neutrophilic dermatoses (pyoderma gangrenosum, pyostomatitis vegetans), and other disorders (isolated reports of pemphigus vulgaris, pemphigus vegetans, acute generalized exanthematous pustulosis, fixed drug eruption, erythema multiforme/Stevens-Johnson syndrome, Henoch-Schönlein purpura, and urticarial vasculitis).(1)

“Some, they may go for cocaine. I’m sure that if I took even one sniff. It would bore me terrifically too. Yet, I get a kick out of you ”

─ Reno Sweeney from Cole Porter’s “Anything Goes”

Plasma cell mucositis (PCM) is a benign polyclonal plasma cell proliferative disorder of the mucous membranes with an unknown etiology. PCM can affect the oral cavity, the nasal mucosa, nasopharynx, larynx, oropharynx, and esophagus, presenting as erythema or a cobblestone, nodular, papillomatous, granular, or velvety surface.(2) Dermatologists may be most familiar with Zoon balanitis as an example of PCM.(3)

Cocaine-induced plasma cell orificial mucositis (CPCOM) is a recently described disorder that has been increasingly reported. Udondo González Del Tánago et al. described the initial case of a 60-year-old man who presented with a one-month history of an exudative ulcerated lesion with raised and infiltrated erythematous edges extending from the left nasal mucosa onto the upper lip. The clinical differential diagnosis included infection (leishmaniasis, syphilis, Lyme disease, and rhinoscleroma), IgG4-related disease, eosinophilic granulomatosis with polyangiitis, neoplasia, eosinophilic angiocentric fibrosis, plasma cell mucositis, and consumption of cocaine. Histological examination revealed a dense inflammatory infiltrate of numerous plasma cells without atypia intermixed with fewer eosinophils in the dermis. A thorough work-up for the disorders listed in the differential diagnosis was negative, except a positive drug screen for cocaine. The lesion resolved with prednisone.(4)

Fernandez-Flores et al. reported the second case of CPCOM in a 56-year-old man who presented with progressive thickening of the nostrils and upper lip over the course of a year. This case did not respond to corticosteroid treatment; however, the authors note that there was prolonged snorting of cocaine (it is not clear if the patient discontinued cocaine after the diagnosis of CPCOM was rendered). The authors suggested the term “cocaine-induced plasma cell orificial dermatomucositis” to underscore the dermal involvement of the lip.(5)

Viedma-Martinez et al. performed a retrospective case series of patients with CPCOM (which they referred to as cocaine-associated plasma cell orificial mucositis — until we know the etiology of this disorder, I think this is the preferable term). A total of 10 patients (6 [60%] male; median [range] age, 45.5 [36-66] years) presented with exudative ulcerated plaques. The lesions had raised and erythematous edges over the nostril and a median (range) evolution time of nine (2-24) months. Septal or palate perforations were observed in four (40%) of the patients. Biopsies revealed a dense inflammatory infiltrate of plasma cells without atypia in the dermis; eosinophils were observed, but there were no neutrophilic infiltrates, vasculitides, or granulomas. Three patients were positive for c-ANCA. All patients reported recent cocaine use. Three urine tests detected cocaine but found no presence of amphetamines or opiates. Six patients improved with corticosteroid therapy. Up to 60% of patients were lost to follow-up.(6)

The cause of CPCOM is unknown, as Fernandez-Flores et al. aptly state: “Another intriguing and mysterious aspect is why this clinically distinct and identifiable presentation has emerged. This suggests the presence of some new additional substance in cocaine used in recent years during the adulteration process.”(5) Presumably, there is a hypersensitivity reaction to cocaine or its unidentified adulterants, including levamisole, that results in local immunodysregulation and plasma cell migration.(6, 7) Although IgG4 has been observed in a subset of patients with CPCOM, further studies are needed to determine if there is any association with IgG4-related disease.(8)

In conclusion, dermatologists should suspect CPCOM in patients with ulcerative lesions of the nose and upper lip. Although the diagnosis is one of exclusion for infectious and neoplastic disorders by biopsy, culture, or PCR, when recognized, most cases will resolve with corticosteroids and avoidance of cocaine.

Point to Remember: Cocaine-induced plasma cell orificial mucositis is a recently described ulcerative disorder of the nose and upper lip, presumably triggered by a yet-to-be-identified antigen and characterized by a hypersensitivity reaction. The diagnosis is rendered by obtaining a history of cocaine use, while ruling out other infectious, autoimmune, or neoplastic disorders. Discontinuation of cocaine and administering corticosteroid therapy is the preferred treatment regimen.

Our expert’s viewpoints

Jeffrey N. Li, MD
Micrographic Surgery and Dermatologic Oncology Fellow
Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston

Though only recently described, enough consistent and visually striking cases of cocaine-induced plasma cell orificial mucositis (CPCOM) have been described in the literature to cement it into the “classical” canon of cocaine-associated dermatoses.

As dermatologists, we pride ourselves on our ability to diagnose rare and complex conditions at a glance, but the various published cases of CPCOM should highlight how important it is to take a complete and thorough history, particularly in lesions that can result in such anatomically destructive sequelae. Suspicion should remain high, particularly in the United States where cocaine use has rebounded significantly since 2011.(9, 10)

A thorough work-up and evaluation should include laboratory evaluations for leishmania, hepatitis, HIV, treponemal organisms, IgG4-related diseases, urine toxicology screening, and a complete blood count with differential. Radiographic and/or endoscopic imaging should be obtained to assess for palatal, nasal septal, or deeper sinus involvement, and multiple biopsies taken for histopathologic evaluation and tissue culture with a broad infectious differential.

It should be noted that though CPCOM shares an anatomic predilection for classically described “cocaine-induced midline destructive lesions” (CIMDLs) caused by direct nasal trauma and vascular ischemia from the cocaine crystals themselves or adulterants, histopathologic analysis of CIMDLs do not demonstrate a pathognomonic pattern, unlike CPCOM.(11) This provides further evidence supporting a distinct pathogenesis, likely resulting from immune dysregulation or a hypersensitivity reaction.

Ronald Berna, MD
Chief Resident in Dermatology
University of Pennsylvania

Misha Rosenbach, MD, FAAD
Dermatology Residency Program Director
University of Pennsylvania

Paul R. Gross, MD, FAAD
Professor of Dermatology
University of Pennsylvania

We recently observed several cases in Philadelphia that are consistent with this entity. In one case, an individual with a longstanding history of cocaine use presented to our hospital for detoxification and was noted to have a large mass on a base of hemorrhagic mucositis protruding from the nasal alae. Biopsy of the mass demonstrated an ulcerated and reactive squamous mucosa with spongiosis; the underlying stroma had superficial granulation tissue rich in plasma cells. Infectious studies on the patient’s tissue and blood were all unremarkable. The patient was transferred to drug rehabilitation per her request and lost to follow up. In another case, an individual with a long history of autoimmune blistering disease was noted to have recurrent perinasal ulcerative mucositis. The patient adamantly denied intranasal drug use, but given high clinical suspicion a urine drug screen was ordered; it was positive for cocaine. Cessation of cocaine use and a rapid prednisone taper led to complete resolution of these lesions without scarring.

We appreciated the recent publications highlighted above, as those representative photos helped us make these diagnoses in our patients. The occurrence of these two cases, both observed within one week at our institution, raises concern that there may be new adulterants or other changes to the cocaine supply in the region. Dermatologists at least in the mid-Atlantic, and likely elsewhere, should be aware of and thinking about this entity.

References

1. Sánchez-Puigdollers A, Just-Sarobé M, Pastor-Jané L. Cutaneous and Mucosal Conditions Associated With Cocaine Use. Actas Dermosifiliogr. 2023 Feb;114(2):125-131. English, Spanish. doi: 10.1016/j.ad.2022.09.005. Epub 2022 Sep 14. PMID: 36115385.

2. Shanahan D, Shipley D, Staines K. Plasma Cell Mucositis. Ear Nose Throat J. 2020 Jul;99(6):NP64-NP65. doi: 10.1177/0145561319849001. Epub 2019 May 9. PMID: 31072192.

3. Heymann WR. Men in the twilight Zoon. Dermatology World Insights and Inquiries. Feb. 19, 2020, Vol. 2, No. 7. www.aad.org/dw/dw-insights-and-inquiries/2020-archive/february/men-in-the-twilight-zoon.

4. Udondo González Del Tánago B, Jiménez-Gallo D, Navarro-Navarro I, Catalina-Fernández I, Ríos-Martín JJ, Linares-Barrios M. Cocaine-induced plasma cell orificial mucositis. J Eur Acad Dermatol Venereol. 2023 Feb;37(2):e244-e245. doi: 10.1111/jdv.18619. Epub 2022 Oct 14. PMID: 36177500.

5. Fernandez-Flores A, González Montero JM. Cocaine-Induced Plasma Cell Orificial "Dermatomucositis": A More Accurate Descriptive Term for a Clearly Dermatological Entity. Am J Dermatopathol. 2024 May 1;46(5):305-308. doi: 10.1097/DAD.0000000000002684. Epub 2024 Mar 12. PMID: 38513123.

6. Viedma-Martinez M, Gallo-Pineda G, Recio-Monescillo M, Jimenez-Gallo D, Lopez-Sanz P, Drake-Monfort M, Urigoitia-Ugalde P, Martínez-Signes V, Llorca-Juan D, Fuertes-Vega L, Ríos-Viñuela E, Escario-Travesedo E, Ríos-Martín JJ, Requena-Caballero L, Linares-Barrios M. Retrospective Case Series of Cocaine-Associated Plasma Cell Orificial Mucositis. JAMA Dermatol. 2024 Mar 1;160(3):320-327. doi: 10.1001/jamadermatol.2023.5692. PMID: 38265770; PMCID: PMC10809139.

7. Tordjman L, Li JN, Villada G. Non-Healing Nasolabial Ulcerated Plaque: A Clinicopathologic Challenge. Int J Dermatol. 2025 Dec;64(12):2201-2203. doi: 10.1111/ijd.70015. Epub 2025 Aug 16. PMID: 40817707; PMCID: PMC12605620.

8. Reyes Albaladejo F, Mansilla-Polo M, Botella-Estrada R. Cocaine-Induced Dermatomucositis: Clarifying Diagnostic Controversies and Introducing IgG4 Positivity as a New Histopathological Feature. Dermatol Ther (Heidelb). 2025 Nov;15(11):3125-3142. doi: 10.1007/s13555-025-01512-0. Epub 2025 Aug 19. PMID: 40830329; PMCID: PMC12549497.

9. Mustaquim D, Jones CM, Compton WM. Trends and correlates of cocaine use among adults in the United States, 2006-2019. Addict Behav. 2021;120:106950. doi:10.1016/j.addbeh.2021.106950.

10. Cano M, Oh S, Salas-Wright CP, Vaughn MG. Cocaine use and overdose mortality in the United States: Evidence from two national data sources, 2002-2018. Drug Alcohol Depend. 2020;214:108148. doi:10.1016/j.drugalcdep.2020.108148.

11. Iorio L, Davanzo F, Cazzador D, et al. Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations. J Clin Med. 2024;13(17). doi:10.3390/jcm13175116.

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