Oral Doxycycline as an alternative initial treatment for desquamative gingivitis
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1
University of Turin, Department of Oncology - Oral Medicine and Oral Oncology Unit, Italy
Introduction
Tetracyclines are chemotherapeutic agents, with a broad spectrum of antibiotic action, but other than this, they are able to inhibit chemiotaxis, phospholipase A2, pro-inflammatory cytokines and metalloproteinases and also to increase the collagen production. Such anti-inflammatory and host-modulating properties favored a large use of tetracyclines in dermatology for inflammatory or immune-mediated diseases. Particularly doxycycline monohydrate, a semisynthetic derivative of tetracycline, has a peculiar ability to suppresses leukocyte chemotaxis and to function as a host-modulating drug.
When used in dermatology, if compared to systemic steroids, tetracyclines are considerably safer in the long term so that their use could be suggested in patient with advanced age, co-morbidities or other contraindications to a long term steroid therapy.
The potential use of tetracycline for mucous membrane pemphigoid (MMP) affecting the oral cavity as the solely in-volved mucous membrane was already reported in 2002 by the First International Consensus1. More recently, a RCT found that starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in Bullous Pemphigoid (BP)2. The current diagnostic criteria for MMP require positive immunologic tests in order to confirm the autoimmune pathogenesis of the sub-epithelial detachment, so that some patient with a clinical phenotype of desquamative gingivitis (DG) suggestive for immune-mediated disease could not reach a definite diagnosis for autoimmune blistering disease. In the literature there is no evidence about the management of these pa-tients.
Thus the current evidence could suggest a potential use of doxycycline in the treatment of patients affected from DG even in absence of a definite diagnosis of immune-mediated disease.
Materials and Methods
We describe two patients with DG, clinically suggestive for Mucous Membrane Pemphigoid (MMP) where a definite diagnosis of immune-mediated blistering disease was not achieved through immunologic tests: negative results to Direct Immunofluorescence (DIF) or ELISA test. In presence of an exclusive gingival involvement with an intense inflammatory status and lacking a definitive diagnosis of MMP an initial treatment with oral doxycycline was preferred to the first-line treatment with topical clobetasol propionate.
Results.
Case 1: a 73 years old female was referred to our clinic by her dentist because of painful gingival bleeding non responsive to scaling and root planing. Her medical history was positive for hypertension, arrhythmia and diabetes; she was assuming ramipril, atenolol, potassium, apixabam, metformin, glimepiride, pantoprazole, delorazepam and vit B12; she also wore a pace-maker.
At intra oral examination she presented DG mainly involving the upper gingiva, she had intense erythema, diffuse small gingival erosions with positive Nikolsky sign, and one single palatal erosion contiguous to the right posterior teeth. An advanced chronic periodontitis potentially inducing per se an inflammatory status was also observed. The patient did not report any other skin, eye or genital lesions.
An incisional biopsy was performed in order to confirm a clinical diagnosis of immune-mediated blistering disease. Even in presence of a histological subepithelial split, DIF was negative. Similarly the ELISA test failed to identify Ab anti BP180 and anti BP230, with Ab anti BP180 just approaching significant values. In presence of an intense gingival inflammatory involvement and lacking a definitive diagnosis of autoimmune disorder, oral doxycycline (200 mg/die for 6 weeks) was prescribed in order to take advantage of its anti-inflammatory, host-modulating and antibacterial effect.
After 3 weeks the palatal erosion had completely resolved and the gingiva showed a partial remission, with an almost 50% reduction in lesion size. The patient reported fluctuating symptoms with partial improvement. No adverse effects were reported.
After 6 weeks, control of disease activity was achieved, no new inflammatory lesions were observed or reported by the patient and pre-existing erosions were on healing. A positive Nikolsky sign was still observed on limited gingival areas. The patient reported mild occasional symptoms. Treatment was continued for adjunctive 6 weeks.
Case 2: a slightly symptomatic DG was occasionally observed in a 80 years old male referring to our clinic for a dental extraction. The patient had hypertension and his medical history was positive for renal transplantation performed 18 years before and myocardial infarction occurred 8 years before. Therefore he was on cyclosporin (75 mg daily), mycophenolic acid (360 mg two times a day), furosemide, aspirin, clopidogrel, metoprolol, clonidine, nitroglycerin, atorvastatin and calcitriol.
At intra oral examination he presented generalized DG and erythema, involving both the upper and lower gingiva, with positive Nikolsky sign, with no other lesions of the oral mucosa. He had poor oral hygiene, with calculus and plaque deposits, and multiple residual roots.
The patient did not report any other skin, eye or genital lesions.
Because of both the dual antiplatelet therapy and the high degree of gingival inflammation favouring bleeding, an incisional biopsy was not immediately performed. A scaling session was scheduled, the physician who prescribed the dual antiplatelet therapy was asked for the possibility to just have a single antiplatelet therapy in order to plan the biopsy sampling and the ELISA test for Ab anti BP-180 and BP-230 was requested.
he prescriber did not support a change of the antiplatelet therapy; in the meantime, the ELISA test was performed with completely negative results. Therefore, as the patient was already on immunosuppressant therapy and in the light of the only presence of gingival involvement, the incisional biopsy was postponed and oral doxycycline (200 mg/die for 6 weeks) was started.
After 6 weeks disease control was achieved, with complete absence of erosions or erythema and the patient entered a consolidation phase. The patient did not report any adverse effects.
Discussion
The International Consensus held in 2002 considered MMP patients with disease occurring in only oral mucosa or oral mucosa and skin as “low-risk” patients due to a lower tendency of scarring. Therefore, a conservative approach was recommended. Topical corticosteroid of moderate to high potency were suggested as the initial treatment and oral prednisone (with or without an immunosuppressive) was to be used only in absence of a satisfactory clinical response. Within such a context of a first-line symptomatic, rather than immunosuppressive treatment, tetracycline hydrochloride was cited as useful is some cases.
As early as 1990, Ronbeck described 14 patients with DG (6 lichen planus, 4 MMP, 1 erythema multiforme and 3 patients with just a descriptive histologic diagnosis) treated with doxycycline monohydrate, 100 mg daily for 4 to 11 weeks3. He reported significant improvements in absence of relevant side effects. More recently, in 2009 Carrozzo et al reported systemic minocycline as a therapeutic option in predominantly oral MMP. Finally, based on the results of the RCT investigating BP published in 20172, it has been hypothesized to introduce doxycycline initially in combination with potent topical steroids, leaving systemic steroids as a second-line option in case of inadequate disease control.
Co-occurrence of periodontitis and immune-mediated DG, mainly MMP, is documented but it still represents a controversial issue. It has been hypothesized that the locally generated inflammatory process associated with periodontitis could trigger and perpetuate the autoimmune response (eg, by enhanced presentation of antigenic epitopes in the damaged periodontium). In DG it is seldom observed that MMP lesions are related to the presence of teeth while edentulous regions are free of disease. In other cases, DG resolved after teeth removal. Irrespective of such clinical observations the potential link between immune-mediated gingivitis and periodontitis remains to be clarified.
Facing the most recent evidences on MMP and the potential link between DG and inflammation due to a poor periodontal status, the use of doxycycline as a first-line therapy could well be hypothesised when a clinical phenotype of MMP is not finally confirmed by either characteristic DIF test findings or by the detection of circulating autoantibodies.
If systemic steroids are a recognized second-line therapy in case of solely oral MMP in favor of topical steroids, wouldn’t it seem reasonable to have topical steroids as a second-line in case of DG associated to intense inflammation but lacking a definite diagnosis in favor of oral doxycycline?
Conversely, in presence of a definite MMP diagnosis, oral doxycycline could be considered an interesting adjunct to topical steroids in presence of an intense inflammatory status, maybe related to poor periodontal conditions, or in case of poor compliance with topical steroid therapy.
References
1 Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, et al. The first international consensus on mu-cous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indica-tors. Arch Dermatol 2002 Mar;138(3):370-9.
2 Williams HC, Wojnarowska F, Kirtschig G, Mason J, Godec TR, Schmidt E, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. The Lancet 2017 2017/04/22/;389(10079):1630-8.
3 Ronbeck BA, Lind PO, Thrane PS. Desquamative gingivitis: preliminary observations with tetracycline treatment. Oral surgery, oral medicine, and oral pathology 1990 Jun;69(6):694-7.
Keywords:
Desquamative gingivitis,
Mucous membrane pemphigoid,
Doxycycline,
oral mucosa,
Treatment
Conference:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.
Presentation Type:
Poster Presentation
Topic:
Oral Diseases
Citation:
Campolongo
M,
Val
M,
Lupatelli
M,
Gandolfo
S and
Pentenero
M
(2019). Oral Doxycycline as an alternative initial treatment for desquamative gingivitis.
Front. Physiol.
Conference Abstract:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine..
doi: 10.3389/conf.fphys.2019.27.00036
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Received:
01 Nov 2018;
Published Online:
09 Dec 2019.
*
Correspondence:
Prof. Monica Pentenero, University of Turin, Department of Oncology - Oral Medicine and Oral Oncology Unit, Turin, Piedmont, 10124, Italy, monica.pentenero@unito.it