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Plasma cell mucositis

Author(s): Reuben Martin-Hendrie, Oral Medicine Registrar and Hadleigh Clark, Oral Medicine Specialist, Hospital & Specialist Dentistry, Auckland District Health Board, New Zealand. Copy edited by Gus Mitchell. May 2022


What is plasma cell mucositis?

Plasma cell mucositis is a rare, benign, inflammatory disorder of the upper aerodigestive tract that shares clinical and histologic features with plasma cell (Zoon) balanitis/vulvitis.  

Plasma cell mucositis most commonly affects the oral mucosa and gingiva. Although it is typically painful with potential oral and oropharyngeal functional consequences, it can also be asymptomatic

The condition has been known by multiple terms, including plasma cell orificial mucositis, idiopathic plasmacytosis, mucous membrane plasmacytosis of the upper aerodigestive tract, and oral papillary plasmacytosis. When limited to the lips, it is referred to as plasma cell cheilitis. Plasma cell gingivitis is a related condition, with exclusive gingival involvement. While concomitant oral and genital or cutaneous involvement has been described, it is exceedingly rare.

Plasma cell mucositis

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Who gets plasma cell mucositis?

Fewer than eighty cases have been reported. Accurate prevalence and incidence data is therefore scarce. Approximately half of cases described involve the oral mucosa. 

Plasma cell mucositis has a slight male predominance (1.2:1) with onset typically after the fourth decade. In the majority of cases, affected individuals have associated autoimmune or immunologically-mediated disease.

Since the early 2000s, an association between khat (qat) chewing and plasma cell mucositis has been observed. Khat is a plant (Catha edulis) endemic to the Eastern peninsula of Africa and Arabia. The leaves are chewed as part of cultural practice; the alkaloid cathinone produces stimulant and euphoric effects. The W.H.O. has classified khat as a drug of abuse and in many countries it is a controlled substance. 

What causes plasma cell mucositis?

The cause of plasma cell mucositis is unknown. It has been postulated that an immune response may develop in susceptible individuals to an as-yet-unidentified infectious trigger (eg, Candida albicans, herpes simplex virus), actinic damage (of the lips), or contact sensitisation

Plasma cell gingivitis appears to be a distinct variant presenting as a localised hypersensitivity reaction of the gingivae to flavouring agents (typically cinnamon and cinnamaldehydes) in toothpaste and chewing gums. Compared to plasma cell mucositis, which may be of insidious onset, plasma cell gingivitis typically arises abruptly (weeks/months) in response to the offending agent, with equally rapid resolution on agent withdrawal.

What are the clinical features of plasma cell mucositis?

  • Symptoms can include oral pain (burning), itch, dysphagia, sore throat, and vocal hoarseness in the initial stages of the disease.
  • Bright red, velvety or glistening erythematous oral mucosal macules, patches, and plaques.
    • May have warty, nodular, granular, or cobblestone surface changes.
  • Gingival involvement can appear “strawberry-like”, similar to granulomatosis with polyangiitis.
    • Both spontaneous and provoked gingival bleeding (ie, to toothbrushing) are commonly described by patients
  • Papillary hyperplasia of the lips may clinically mimic squamous cell carcinoma or orofacial granulomatosis (cheilitis granulomatosa).
  • Other commonly affected intraoral sites include the palatal and buccal mucosa.
  • Diffuse, sloughing, or vegetative oral ulceration can occur, as can contact bleeding associated with tissue hyperaemia or superimposed candidal infection.
  • Both upper and lower airways involvement can lead to strictures.
  • It may also affect nasal, pharyngeal, laryngeal, tracheal, bronchial, and oesophageal mucosa. 

What are the complications of plasma cell mucositis?

  • Oral hygiene impairment leading to increased dental plaque, further exacerbating oral inflammation and periodontal disease.
  • Laryngeal and airway strictures:
    • Difficulties in speaking, with vocal hoarseness
    • Compromised airways with stridor, wheeze, or dyspnoea. 

To date, no cases have evolved to plasma cell neoplasms

How is plasma cell mucositis diagnosed?

Diagnosis can be challenging and requires a high index of suspicion, alongside clinicopathologic correlation.

Dependent on the distribution and surface morphology of involved sites, initial blood and microbiologic testing may include studies to exclude immunobullous (e.g. skin autoantibodies), granulomatous (e.g. sACE), infectious (e.g. fungal swabs, treponemal serology) and autoimmune (e.g. coeliac serology, ANA, ANCA, C3/C4, IgG subclasses) processes. When contact reactions are suspected, patch testing may be considered. 

Tissue biopsy reveals a dense subepithelial infiltrate of mature plasma cells and pseudoepitheliomatous hyperplasia, Russell body formation, and secondary microabscess formation may be noted.

Adjunctive immunohistochemical (CD138) and immunoperoxidase (kappa and lambda in situ hybridisation) techniques are used to confirm polyclonality. Both cell markers on fresh-submitted tissue and complementary serology (immunoglobulins, serum protein electrophoresis, serum-free light chains), urinary Bence Jones proteins, and peripheral flow cytometry may be undertaken to further exclude underlying plasma cell dyscrasia. 

What is the differential diagnosis for plasma cell mucositis?

The differential diagnosis of plasma cell mucositis is broad and dependent on both oral mucosal distribution and morphologic characteristics. It may include consideration of: 

What is the treatment for plasma cell mucositis?

General measures

  • Food and oral product diaries to identify aggravating factors (foods, oral care products, cosmetics).
  • Oral hygiene should be encouraged with a gentle toothbrush/mouth swab and consideration given to low-flavour and SLS-free toothpaste to facilitate this.
  • Oral inflammation may predispose to candidal and bacterial infection, which can be managed with antiseptic mouthwash (e.g. chlorhexidine mouth rinse), topical antifungals, and/or antibiotics (e.g. beta-lactam, nitroimidazoles).

Specific measures

There is no consensus on the treatment for plasma cell mucositis.

First-line therapy is often:

Other treatments that have been used in recalcitrant cases include:

Given the often synchronous or metachronous presentation with other aerodigestive tract involvement, referral for nasendoscopy/bronchoscopy should be considered for any patient with phonation or breathing difficulties to exclude airway involvement.

What is the outcome for plasma cell mucositis?

Plasma cell mucositis is generally considered to be a benign condition with a favourable prognosis and no significant complications. Spontaneous resolution has been described, although this is slow and protracted.

Treatment is aimed at stabilisation of the disease; close clinical follow up is recommended.

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  • Antonelli A, Averta F, Diodati F, et al. An Uncommon Case of Plasma Cell Mucositis of the Tongue in a Young Man. Case Rep Dent. 2020;2020. doi:10.1155/2020/3429632. Journal
  • Arun K, Ambooken M, Varghese S, Varghese T, Mathew J. A rare case of plasma cell mucositis in a young patient. J Indian Soc Periodontol. 2017;21(1):63. doi:10.4103/jisp.jisp_335_15. Journal
  • Galvin S, Bowe C, Regan EM, Conlon N, Flint SR, Healy CM. Circumorificial plasmacytosis/plasma cell orificial mucositis: a case series and a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122(3):e77–e81. doi:10.1016/j.oooo.2016.05.014. Journal
  • Solomon LW, Wein RO, Rosenwald I, Laver N. Plasma cell mucositis of the oral cavity: report of a case and review of the literature. Oral Surg, Oral Med, Oral Pathol, Oral Radiol. 2008;106(6):853–860. doi:10.1016/j.tripleo.2008.08.016. Journal 
  • Tailor A, Pemberton MN, Murphy R, Hegarty AM. Plasma cell mucositis related to qat chewing: a report of 2 cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;131(3):e65–e70. doi:10.1016/j.oooo.2020.09.009. Journal
  • Triplett J, Hee G, McLean-Tooke A, Lucas M. Long-term control of laryngeal plasma cell mucositis with systemic immunosuppression. BMJ Case Rep. 2018;2018. doi:10.1136/bcr-2017-221333. Reports

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