Table of Contents  
CASE REPORT
Year : 2012  |  Volume : 4  |  Issue : 1  |  Page : 64-69

Mucous membrane pemphigoid with exclusive gingival involvement: Report of a case and review of literature


1 Department of Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, India
2 Department of Oral Medicine and Radiology, Z.A Dental College and Hospitals, A.M.U, Aligarh, Uttar Pradesh, India

Date of Web Publication10-Sep-2012

Correspondence Address:
Shamimul Hasan
C/O Mr. Mohd. Javed Khan, C-4, Duplex Quarters (New), Sir Syed Nagar, Aligarh - 202 002, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-8844.99884

Rights and Permissions
  Abstract 

According to Sir William Osler, Mouth is the mirror of the body which reflects systemic ­diseases. The oral mucosa may be affected by a variety of mucocutaneous diseases and oral lesions may occur first or very early in several mucocutaneous disorders. The erosive gingival lesions associated with vesiculobullous diseases such as lichen planus, cicatricial pemphigoid, and pemphigus vulgaris have been collectively referred to as "Desquamative gingivitis" (DG). Gingival desquamation is a clinical sign in which the gingiva appears reddish, painful, glazed and friable with destruction of the epithelium. This gingival desquamation is due to various disease processes in gingiva. The disease process may be a localized disease of gingiva or a systemic disease which manifests in the gingiva. It is important to be aware of this rare clinical entity so as to distinguish DG from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental surgeon. Accurate diagnosis and effective treatment of these lesions may greatly diminish or reverse disease progression. Here by, we present a case of mucous membrane pemphigoid presenting as gingival desquamation in a 45 year old female. Our patient presented with generalized erythematous gingiva and gingival desquamation involving the free, attached and marginal gingiva of left maxillary and mandibular dentition. However, other mucosal and skin involvement was not appreciated in the present case. Thorough history, clinical examination, histopathology and immunofluorescence studies helped us to arrive at the diagnosis of this rare sub-epithelial blistering disorder.

Keywords: Corticosteroids, desquamative gingivitis, mucous membrane pemphigoid, Nikolsky′s sign


How to cite this article:
Hasan S, Kapoor B, Siddiqui A, Srivastava H, Fatima S, Akhtar Y. Mucous membrane pemphigoid with exclusive gingival involvement: Report of a case and review of literature. J Orofac Sci 2012;4:64-9

How to cite this URL:
Hasan S, Kapoor B, Siddiqui A, Srivastava H, Fatima S, Akhtar Y. Mucous membrane pemphigoid with exclusive gingival involvement: Report of a case and review of literature. J Orofac Sci [serial online] 2012 [cited 2017 Apr 27];4:64-9. Available from: http://www.jofs.in/text.asp?2012/4/1/64/99884


  Introduction Top


Oral mucocutaneous conditions are a group of disorders which are observed in the dental practice. Oral mucosal manifestations may be the initial feature, or the only sign of such diseases. In other cases, lesions occur in both the skin and mucosae, with several clinical manifestations involving the tissues. [1] Mucocutaneous lesions are non-plaque induced gingival lesions and constitute a subgroup of gingival manifestations of systemic conditions. All these disorders share two features in common: an immune-mediated pathogenesis and possibly common clinical appearance. This common clinical appearance is called 'Desquamative gingivitis' (DG). DG is a clinically relevant entity because it can affect oral health and can be a feature of systemic disease. There is no evidence that DG per se can cause attachment loss and alveolar bone destruction. [2] As opposed to plaque induced gingivitis, DG is more common in middle aged to elderly females, is painful, affects the buccal or labial gingival predominantly, frequently spares the marginal gingival but can involve the whole thickness of the attached gingiva and its clinical appearance is not significantly altered by traditional oral hygiene measures or conventional periodontal therapy alone. [3] Chronic desquamative gingivitis was first described by Tomes and Tomes in 1894. [4] is a descriptive term, first introduced by Prinz in 1932 that indicates the presence of erythema, desquamation, erosion, and blistering of attached and marginal gingiva. [5] DG is not considered a definitive diagnosis because it is a clinical manifestation of several disorders, as suggested by Glickman and Smulow in 1964 [6] and confirmed recently by others. [7] The main characteristics of DG is an extensive desquamation and / or erosion of the buccal aspect of attached gingival of anterior teeth. [8] DG is now recognized to be mainly a manifestation of a number of disorders ranging from vesiculobullous diseases to adverse reactions to a variety of chemical or allergens. [3] Overall, Mucous membrane pemphigoid, Oral lichen planus, and Pemphigus vulgaris are the most common causes of DG, with the first two accounting for about 80% of cases. [3] Use of clinical and laboratory parameters have revealed that approximately 75% of DG cases have a dermatologic genesis . However, many of these autoimmune conditions do present with oral manifestations primarily. [9] Nisengard and Levine [10] cited the following as the standard in making a clinical diagnosis of DG: (a) Gingival erythema not resulting from plaque, (b) gingival desquamation, (c) other intraoral and sometimes extraoral lesions, and (d) complaint of sore mouth, particularly with spicy foods. Hence it is of utmost importance to identify the disease responsible for DG to establish appropriate therapeutic approach and management.


  Case Report Top


A 45 year old female patient reported to the department of Oral medicine and Radiology with a complaint of burning sensation and tenderness in the gums on intake of spicy food for the past 9 months. The patient had also noticed the formation of blisters on the gums on and off which would break off on their own. The medical history was not significant and she was otherwise in good health. There were no associated ocular, cutaneous or genital lesions. Intraoral examination revealed generalized erythematous and inflammed labial and buccal gingiva [Figure 1]. There was an area of desquamation involving the buccal aspect of free, marginal and attached gingiva in relation to 23, 24, 25, 26, 27, 33, 34, 35, 36 and 37 [Figure 2]. Gentle manipulation of the normal mucosa induced a positive Nikolsky's sign. Erosions were noticed involving the marginal and attached gingiva in relation to 13, 46 [Figure 3]. The patient's oral hygiene was fair and gingiva showed bleeding on probing with no attachment loss. Faint grey-white striae could be seen bordering the desquamated area in some part [Figure 3]. Considering a history of burning sensation with formation of on and off blisters, and oral examination revealing generalized erythematous gingiva, with desquamative gingivitis, positive nikolsky's sign and areas of erosions, provisional diagnosis of Desquamative gingivitis due to vesiculo-bullous disorder was given. Differential diagnosis included mucous membrane pemphigoid, bullous pemphigoid, pemphigus vulgaris and bullous lichen planus. After an informed consent from the patient, an incisional biopsy was taken from the perilesional gingival tissue for histopathologic and immunofluorescent studies. Histopathological picture showed parakeratinised stratified squamous epithelium of variable thickness along with presence of subepithelial cleft and basal cell degeneration in few areas. Connective tissue stroma showed band of intense chronic inflammatory cells (plasma cells) along with areas of vascularity and hemorrhage [Figure 4] and [Figure 5]. Direct immunofluorescence showed a linear deposition of IgG and C3 at the dermo-epidermal junction. Final diagnosis of Mucous membrane pemphigoid was made based on the clinical, histopathological and immunofluorescent interpretations. The patient was subjected to thorough oral prophylaxis and oral hygiene instructions. Thereafter, the patient was prescribed topical application of medium potency steroids (flucinonide 0.01% Lidex) 3-4 times daily for one month and vitamin B complex supplements. The patient was reviewed every 2 weeks for the first one month. The lesions improved considerably with topical steroids within 4 weeks of starting the treatment. The frequency of topical steroid application was tapered to once daily application for the next 15 days. The patient was asked to stop the topical application and reinforcement of oral hygiene instructions was given. Since the lesions can recur, the patient was under observation for one year and there was no recurrence.
Figure 1: Generalised erythematous and inflammed labial and buccal gingiva

Click here to view
Figure 2: Desquamative gingivitis involving free, marginal and attached gingiva of left maxillary and mandibular teeth. Arrows depicting the areas of desquamation of gingiva

Click here to view
Figure 3: Positive Nikolsky's sign in relation to 13 and 46. Arrows depicting erosive lesion and faint white striae in relation to 43,44

Click here to view
Figure 4(a,b): Histopatholgy showing sub-epithelial cleft and basal cell degeneration, along with chronic inflammatory cells and hemorrhagic areas

Click here to view
Figure 5: Direct immunofluorescence showing a linear deposition of IgG and C3 at the dermo-epidermal junction

Click here to view



  Discussion Top


Mucous membrane pemphigoid is a chronic autoimmune sub-epithelial disease that primarily affects the mucous membranes of patients over the age of 50 years, resulting in mucosal ulceration and subsequent scarring. [11] The condition is also known as cicatricial pemphigoid, benign mucous membrane pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid. [12] However, in reporting the results of the First International Consensus on Mucous membrane pemphigoid, Chan and others [12] recommended the term "mucous membrane pemphigoid" because the disease may not be benign when it causes blindness from ocular involvement or death from laryngeal scarring; [13] it may not be scarring, as in gingival involvement; and it may affect a number of mucous membranes such as the oral and nasal mucosa, pharynx, anus, genital mucosa, esophagus and trachea.

The incidence of MMP has been estimated to be between 1.5 to 9.6 cases per 100,000 / year. [14] It appears to manifest more commonly in females than males at a ratio of 2:1 and in an estimated 83% to 100% of cases, the oral cavity is involved. [12] The mean age of onset is 50 years or older. However, case reports of mucous membrane pemphigoid in children and adolescents exist. [15]

The primary lesion of MMP occurs when autoantibodies directed against proteins in the basement membrane zone, acting with complement (C3) and neutrophils cause a sub-epithelial split and subsequent vesicle formation. The antigens associated with MMP are most frequently present in the lamina lucida portion of the basement membrane, but recent research has demonstrated that the identical antigen is not involved in all cases, and the lamina densa may be the primary site of involvement in some cases. The majority of cases of MMP demonstrate IgG directed against antigens on the epidermal side of the salt-split skin, which have been identified as BP180 (also called type XVII collagen); however, cases of MMP have also been identified where the antigen is present on the dermal side of the split. This antigen has been identified as epiligrin laminin 5). [11]

The oral cavity usually represents the first and often the only site of disease involvement. Intraoral manifestations of mucous membrane pemphigoid include desquamative gingivitis, vesiculobullous lesions, and ulcerations. Patients often exhibit a positive Nikolsky' sign with epithelial sloughing and exposure of painful bleeding surfaces beneath. Periods of exacerbation and remission are common, although some lesions may remain unrelenting for years. [16],[17] The gingiva is by far the most common intraoral site affected, [18],[19] and the lesions tend to heal with insignificant scarring. DG is the main oral feature of MMP [20] and may be the presenting feature. [21] Most cases appear to be related to mucous membrane pemphigoid, but lichen planus is also a common cause. [22],[23] DG is a fairly common disorder in which the gingivae are desquamated. Chronic soreness is common and can be worse with the intake of spicy foods. [24] The clinical appearance is of gingival erythema and loss of stippling, extending apically from the gingival margins to the alveolar mucosae. The desquamation may vary from mild, almost insignificant small patches to widespread erythema [17],[25] with a glazed appearance.

In severe cases, adhesions may develop between the buccal mucosa and the alveolar process, around the uvula and tonsillar fossae, and between the tongue and the floor of the mouth. When lesions involve the frenulum, ankyloglossia or limited mobility of the tongue may result.

The conjunctiva is the second most common site of involvement and can lead to scarring and adhesions developing between the bulbar and palpebral conjunctiva called symblepharon. Corneal damage is common, and progressive scarring leads to blindness in close to 15% of patients. Lesions may also affect the genital mucosa, causing pain and sexual dysfunction. Laryngeal involvement causes pain, hoarseness, and difficulty in breathing, whereas esophageal involvement may cause dysphagia, which can lead to debilitation and death in severe cases. [11] Skin lesions are uncommon and are located on the face, neck, scalp, trunk and extremities. [26]

The patient, in our case report was a female of 45 years of age who presented with exclusive oral involvement without any other mucosal or skin involvement. There was widespread erythema and inflammation of labial and buccal gingiva with no palatal involvement. Desquamation of free, attached and marginal gingiva was appreciable with left maxillary and mandibular teeth. Gentle manipulation of the normal mucosa showed positive Nikolsky's sign. However, the gingiva was firm and resilient in consistency with no attachment loss.

The definitive diagnosis can only be established based on the histopathological data and immunofluorescence studies. Histologically, the disease is characterized by separation at basal membrane level, giving rise to a subepithelial blister. [27] The lamina propria shows a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and neutrophils. [26] Histopathological features in the present case, showed sub-epithelial cleft and basal cell degeneration, along with band of intense chronic inflammatory cells (plasma cells) and areas of vascularity and hemorrhage.

Direct immunofluorescence features of MMP specimen shows a linear deposition of complement (usually C3) and IgG or other immunoglobulins at the basement membrane zone. [28] Intact epithelium and connective tissue are critical in evaluating a specimen with DIF techniques.

Serum IIF testing has been believed to be of little diagnostic value in MMP since circulating basement membrane antibodies are often not detected. [29] The sensitivity of IIF can be improved using normal human skin or mucous membrane incubated with 1mol/l NaCl solution as a substrate, thus separating the epithelium from the connective tissue at the site of lamina lucida (known as salt split). This technique can also help in differentiating between antigens located on the epidermal side (MMP) of the split and those located on the dermal side (EBA) with the provision of additional details for the diagnosis. [11]

Direct immunofluorescence features in our case, showed linear deposition of IgG and C3 at the dermo-epidermal junction.

The factors to be taken into account in treating MMP are its location, severity and progression rate. In low risk patients with lesions confined to the oral mucosa and/or skin, topical corticosteroids are advised, such as 0.1% triamcinolone acetonide, 0.05% fluocinolone acetonide, or 0.05% clobetasol propionate in orabase, applied 3-4 times a day during 9-24 weeks. In patients with isolated erosions, intralesional corticosteroid injections (triamcinolone in 5-10 mg/ml solution) can be used. In subjects presenting gingival lesions in the form of desquamative gingivitis, 0.05% clobetasol propionate is recommended, with nystatin 100,000 IU to avoid candidiasis overinfection. [26],[30] When MMP affects the palate, esophagus or nasal mucosa, beclomethasone dipropionate or budesonide (50-200 μg) can be prescribed. [26] Depending on the patient response, other alternatives can be considered, such as 100 mg of doxycycline a day for 8 weeks, or minocycline 50-100 mg/ day during 3-39 months, and nicotinamide 2-3 g/day. [26],[30] In high risk patients with multiple oral lesions, rapidly progressing spread of the disease to other mucosal membranes such as the eyes, genital, esophagus or nasopharyngeal zone, or recurrent lesions, the administration of prednisone 1-2 mg/kg/day, with gradual dose reduction, and immune suppressors such as cyclophosphamide (0.5-2 mg/kg/day), azathioprine 1-2 mg/kg/day, or mycophenolate mofetil 2-2.5 g/day has been described. [26],[30],[31],[32] Another treatment option is dapsone (50-200 mg/day) for 12 weeks. [32] Treatment is started with 25 mg during three days, followed by 25 mg increments every three days until reaching a dose of 100 mg, followed by boosting of the dosage to 150 mg. [30] Blood test monitoring is important in order to avoid the appearance of side effects. [32] Other drugs that have been used include methotrexate, which at low doses prevents the progression of conjunctival cicatrization in 72% of all patients, tumor necrosis factor-alpha, leflunomide or sulfonamide (regarded as an alternative to dapsone, administered at a dose of 1.5-3 g/day). Less commonly used options in turn are intravenous immunoglobulins (1-2 g/kg/cycle), plasmapheresis in patients with eye lesions refractory to corticosteroids and immune suppressors and, as a last option, surgery to avoid complications such as blindness, esophageal strictures or upper airway stenosis. [26] A case report [33] with 8 years of follow up presented the successful management of a patient with both periodontal disease and MMP through the use of topical corticosteroids and standard periodontal therapy including scaling and root planning and surgical treatment. Recently a case report [34] demonstrated that Low level laser therapy (LLLT) may improve healing after the application of a local corticosteroid for a period of 12 months. The basic principle of LLLT is based on the biostimulation or biomodulation effect, [35] which considers that irradiation at a specific wavelength is able to able to alter cellular behavior.

The patient in the present case underwent thorough oral prophylaxis and was treated with topical steroids and vitamin supplements for one month. The lesions showed dramatic improvement after steroid application. Regular follow up was done and the lesions showed no signs of recurrence.


  Conclusion Top


Mucous membrane pemphigoid presenting as exclusive DG is a rare occurrence. Correct diagnosis of the condition entails taking a detailed history, coupled with a thorough intraoral and extraoral examination, along with histopathology and Immunofluoroscence studies. The gingival lesions are usually treated by improved oral hygiene measures and topical corticosteroid therapy.

 
  References Top

1.Ramirez-Amador VA, Esquivel-Pedraza L, Orozco-Topote R. Frequency of oral conditions in a dermatology clinic. Int J Dermatol 2000;39;501-5.  Back to cited text no. 1
    
2.Tricamo MB, Rees TD, Hallmon WW, Wright JM, Cueva MA, Lemons JM. Periodontal status in patients with gingival mucous membrane pemphigoid. J Periodontol 2006;77:398-405.  Back to cited text no. 2
    
3.Scully C, Porter S. The clinical spectrum of Desquamative gingivitis. Semin Cutan Med Surg 1997;16:308-13.  Back to cited text no. 3
    
4.Tomes J, Tomes G . Dental Surgery. 4 th ed. London: J and A Churchill Ltd; 1894.  Back to cited text no. 4
    
5.Prinz H . Chronic diffuse desquamative gingivitis. Dental Cosmos 1932;74;332-3.  Back to cited text no. 5
    
6.Glickman I, Smulow J . Chronic desquamative gingivitis - Its Nature and treatment. J Periodontol 1964;35:397-405.  Back to cited text no. 6
    
7.American Academy of Periodontology. Oral features of mucocutaneous disorders. J Periodontol 2003;74:1545-56.  Back to cited text no. 7
    
8.Robinson NA, Wray D. Desquamative gingivitis. A Sign of mucocutaneous disorders; A Review. Aust Dent J 2003;48:206-11.  Back to cited text no. 8
    
9.Neville BW, Damm DD, Allen C, Bouquot JE. Dermatologic disease. In: Neville BW, Damm DD, Allen C, Bouquot JE, editors. Oral and Maxillofacial Pathology, Philadelphia: Saunders; 1995.  Back to cited text no. 9
    
10.Nisengard RJ, Rogers RS. The treatment of Desquamative gingival lesions. J Periodontol 1987;58:167-72.  Back to cited text no. 10
    
11.Greenberg MS, Glick M. Burkitts oral medicine diagnosis and treatment. 10 th ed. 2003; p. 72-3.  Back to cited text no. 11
    
12.Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, et al. The first international consensus on mucous membrane pemphigoid: Definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol 2002;138:370-9.  Back to cited text no. 12
    
13.Boedeker CC, Termeer CC, Staats R, Ridder GJ. Cicatricial pemphigoid in the upper aerodigestive tract: Diagnosis and management in severe laryngeal stenosis. Ann Otol Rhinol Laryngol 2003;112:271-5.  Back to cited text no. 13
    
14.Lo Russo L, Fedele S, Guiglia R, Ciavarella D, Lo Muzio L, Gallo P, et al. Diagnostic pathways and the clinical significance of desquamative gingivitis. J Periodontol 2008;79:4-24.  Back to cited text no. 14
    
15.Chang YS, Rees TD, Wright JM, Plemons JM. Childhood oral pemphigoid: A case report and review of the literature. J Oral Pathol Med 2001;30:372-7.  Back to cited text no. 15
    
16.Scott JE, Ahmed AR. The blistering diseases. Med Clin North Am 1998;82:1239-83.  Back to cited text no. 16
    
17.Scully C, Carrozzo M, Gandolfo S, Puiatti P, Monteil R. Update on mucous membrane pemphigoid. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:56-68.  Back to cited text no. 17
    
18.Shklar G, McCarthy PL. Oral lesions of mucous membrane pemphigoid. A study of 85 cases. Arch Otolaryngol 1971;3:354-64.  Back to cited text no. 18
    
19.Silverman S Jr., Gorsky M, Lozada-Nur F, Liu A. Oral mucous membrane pemphigoid. A study of sixty-five patients. Oral Surg Oral Med Oral Pathol 1986;61:233-7.  Back to cited text no. 19
    
20.Fine RM, Weathers DR. Desquamative gingivitis: A form of cicatricial pemphigoid? Br J Dermatol 1980;102;393-9.  Back to cited text no. 20
    
21.Vaillant L, Arbeille B, Goga D, De Muret A, Prime A, Lorette G. Cicatricial pemphigoid disclosed by superficial Desquamative gingivitis: Clinical and immune electron microscopic study of a case. Ann Dermatol Venerol 1990;117;613-20.  Back to cited text no. 21
    
22.Rogers RS, Sheridan PJ, Nightingale SH. Desquamative gingivitis: Clinical, histological, immunopathologic and therapeutic observations. J Am Acad Dermatol 1982;7:729-35.  Back to cited text no. 22
    
23.Sklavounou A, Laskaris G. Frequency of desquamative gingivitis in skin diseases. Oral Surg 1983;56:141-4.  Back to cited text no. 23
    
24.Alkan A, Gunhan O, Alkan A, Otan F. A clinical study of Oral Mucous membrane Pemphigoid. J Int Med Res 2003;31:340- 4.   Back to cited text no. 24
    
25.Bozcurt FY, Celenligil H, Sungur A, Ruacan S. Gingival involvement in mucous membrane pemphigoid. Quintessence Int 1998;29:438-41.  Back to cited text no. 25
    
26.Bagan J, Lo Muzio L, Scully C. Mucosal disease series. Number III. Mucous membrane pemphigoid. Oral Dis 2005;11:197-218.  Back to cited text no. 26
    
27.Schifter M, Yeoh SC, Coleman H, Georgiou A. Oral mucosal diseases: The inflammatory dermatoses. Aust Dent J 2010;55:23-38.  Back to cited text no. 27
    
28.Bean SF, Waisman M, Michel B, Thomas CI, Knox JM, Levine M. Cicatricial pemphigoid: Immunofluorescence studies. Arch Dermatol 1972;106:195-9.  Back to cited text no. 28
    
29.Laskaris G, Demetrios N, Angelopoulos A. Immunofluorescent studies in Desquamative gingivitis. J Oral Pathol 1981;10:398-407.  Back to cited text no. 29
    
30.Scully C, Lo Muzio L. Oral mucosal diseases: Mucous membrane pemphigoid. Br J Oral Maxillofac Surg 2008;46:358-66.  Back to cited text no. 30
    
31.Knudson RM, Kalaaji AN, Bruce AJ. The management of mucous membrane pemphigoid and pemphigus. Dermatol Ther 2010;23:268-80.  Back to cited text no. 31
    
32.López-Jornet P, Bermejo-Fenoll A. Treatment of pemphigus and pemphigoids. Med Oral Patol Oral Cir Bucal 2005;10:410-1.   Back to cited text no. 32
    
33.Damoulis PD, Gagari E. Combined treatment of periodontal disease and benign mucous membrane pemphigoid. Case report with 8 years maintainance. J Periodontol 2000;71:1620-9.  Back to cited text no. 33
    
34.Hasan G, Basak K, Hakan B, Tolga F. Low-level laser therapy in the treatment of Mucous Membrane Pemphigoid: A Promising Procedure. J Periodontol 2010;81:1226-30.  Back to cited text no. 34
    
35.Ozceik O, Cenk Haytac M, Kunin A, Seydaoglu G. Improved wound healing by low level laser irradiation after gingivectomy procedures. A Controlled clinical pilot study. J Clin Periodontol 2008;35:250-4.  Back to cited text no. 35
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed3286    
    Printed82    
    Emailed0    
    PDF Downloaded339    
    Comments [Add]    

Recommend this journal