Journal of Investigative and Clinical Dentistry (2011), 2, 207–211
CASE REPORT
Ligneous gingivitis associated with plasminogen deficiency: a challenge in diagnosis Seunghee Cha, Donald Cohen, Indraneel Bhattacharyya & Joseph Katz Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA
Keywords gingival enlargement, ligneous gingivitis, ligneous periodontitis, plasminogen deficiency, pseudomembrane. Correspondence Dr Seunghee Cha, Department of Oral and Maxillofacial Diagnostic Sciences, College of Dentistry, University of Florida, P.O. Box 100414, Gainesville, FL 32610, USA. Tel: +1-352-273-6687 Fax: +1-352-294-5311 Email: [email protected] Received 22 June 2010; accepted 26 June 2010.
Abstract A 66-year-old female presented with gum bleeding and soreness. Her medical history was significant for delayed wound healing, which appeared to cause blindness in her right eye. A gingival incisional biopsy revealed replacement of fibrous connective tissue by an amorphous and eosinophilic material. Direct immunofluorescent staining for antibodies was negative. After the differential diagnosis of ligneous gingivitis (LG) was rendered, the activity and antigenic level of plasminogen was tested and found to be significantly decreased. Partial improvement was observed within 1 year following a regimen of scaling, gingival curettage, topical steroids, and improved oral hygiene. LG is a rare condition, occurring as a result of plasminogen deficiency and subsequent fibrin accumulation. It presents as pseudomembranous gingiva and might affect the eyes and other organs. Dentists should be familiar with this condition, since they might assist in a diagnosis of this disease, with significant morbidity often missed by medical professionals.
doi: 10.1111/j.2041-1626.2011.00066.x
Introduction Ligneous disease is an unusual form of a chronic and systemic ‘‘idiopathic membranous’’ condition. The word ‘‘ligneous’’ describes a wood-like consistency of a substance that may replace normal mucosa.1 This condition, which affects both males and females at any age, usually occurs as a part of a systemic disorder that involves other mucosal sites, such as the eye (ligneous conjunctivitis), ear, respiratory tract, female genital tract, and kidneys.2 Of the organs affected, gingival tissue is characterized by pseudomembranous, nodular gingival enlargement and periodontal tissue destruction, leading to ligneous gingivitis (LG) and ligneous periodontitis, respectively. Generally, gingival enlargement occurs as a result of a reaction to dental plaque or of exposure to drugs such as phenytoin, cyclosporine, or calcium channel blockers,3 or as part of a systemic syndrome.4 Patients with these conditions have shown marked impairment of wound healing in mucous membranes. Since the major constituent of the pseudomembrane is fibrin(ogen), this raises the possibility of major deficiency ª 2011 Blackwell Publishing Asia Pty Ltd
of (plasmin-mediated) extracellular fibrinolysis in these patients.1 In fact, studies have suggested that hypoplasminogenemia is a common predisposing factor for the development of LG/periodontitis and its associated complications.5–7 We present a rare case of LG associated with plasminogen deficiency and discuss its potential implications. Case report A 66-year-old female presented to the Oral Medicine Clinic at the University of Florida, College of Dentistry (Gainesville, FL, USA) with a chief complaint of constant bleeding, irritation, and soreness of the gums in the molar areas. Her medical history was significant for hypertension treated with lisinopril (Zestril)/hydrochlorothiazide (Hydrodiuril) (20/25 mg/day) and gemfibrozil (Lopid) (600 mg twice a day), peripheral neuropathy treated with gabapentin (Neurontin) (400 mg three times a day), mild arthritis, and glaucoma in her left eye treated with latanoprost ophthalmic solution (Xalatan). She was blind in her right eye as a result of childhood scarring of 207
Pseudomembranous gingiva
the conjunctiva. The patient reported delayed wound healing of skin on her abdomen. On examination, there was no lymphadenopathy or swelling of the neck. The lower lip was erythematous with slight cheilitis, and the tongue was fissured with a scrotal and geographic tongue appearance. The interdental papilla between the right first and second lower molars was ulcerated with significant gingival enlargement and inflammation (Figure 1a). Hypertrophic gum tissue was noted on the upper left molar area (Figure 1b). The gingival tissues on both arches were hypertrophic, especially the maxilla, and exhibited loss of stippling and an uneven hypertrophic surface right above the right upper central incisor (Figure 1c). There was bleeding from the gingival upon palpation. A tentative clinical diagnosis of desquamative gingivitis was made, and the patient underwent an incisional biopsy from the right mandibular buccal gingiva adjacent to the first molar (Figure 1a). Routine microscopic examination revealed inflamed multiple fragments of fibrous tissue surfaced in part by orthokeratinized-stratified squamous epithelium, which exhibited significant thickening of the spinous cell layer with elongated and bulbous rete ridge formation. The most striking feature was replacement of the majority of fibrous connective tissue by the deposition of an amorphous, amyloid-like material (Figure 2a–c). This material contained numerous thin-walled, dilated vascular channels and scattered inflammatory cells. An amyloid stain, namely Congo red, was negative (Figure 2d), while a periodic acid–Schiff stain was positive for the pink material. Antibody staining was granular at the point of the basement membrane (+1 of 4) for C3, and negative for immunoglobulin (Ig)G, IgM, IgA, and fibrinogen. Based on these findings, in combination with the clinical presentation, a diagnosis of LG was rendered. In view of this diagnosis, the patient was referred for a medical work-up. Of significance were the lowered red blood cell count of 3.64 million/lL (reference range: 4.20–5.80 million/lL) and hemoglobin count of 11.4 g/dL (13.2– 17.1 g/dL), increased glucose of 118 mg/dL (65–99 mg/dL) with hemoglobin A1c of 6.2% (
CASE REPORT
Ligneous gingivitis associated with plasminogen deficiency: a challenge in diagnosis Seunghee Cha, Donald Cohen, Indraneel Bhattacharyya & Joseph Katz Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA
Keywords gingival enlargement, ligneous gingivitis, ligneous periodontitis, plasminogen deficiency, pseudomembrane. Correspondence Dr Seunghee Cha, Department of Oral and Maxillofacial Diagnostic Sciences, College of Dentistry, University of Florida, P.O. Box 100414, Gainesville, FL 32610, USA. Tel: +1-352-273-6687 Fax: +1-352-294-5311 Email: [email protected] Received 22 June 2010; accepted 26 June 2010.
Abstract A 66-year-old female presented with gum bleeding and soreness. Her medical history was significant for delayed wound healing, which appeared to cause blindness in her right eye. A gingival incisional biopsy revealed replacement of fibrous connective tissue by an amorphous and eosinophilic material. Direct immunofluorescent staining for antibodies was negative. After the differential diagnosis of ligneous gingivitis (LG) was rendered, the activity and antigenic level of plasminogen was tested and found to be significantly decreased. Partial improvement was observed within 1 year following a regimen of scaling, gingival curettage, topical steroids, and improved oral hygiene. LG is a rare condition, occurring as a result of plasminogen deficiency and subsequent fibrin accumulation. It presents as pseudomembranous gingiva and might affect the eyes and other organs. Dentists should be familiar with this condition, since they might assist in a diagnosis of this disease, with significant morbidity often missed by medical professionals.
doi: 10.1111/j.2041-1626.2011.00066.x
Introduction Ligneous disease is an unusual form of a chronic and systemic ‘‘idiopathic membranous’’ condition. The word ‘‘ligneous’’ describes a wood-like consistency of a substance that may replace normal mucosa.1 This condition, which affects both males and females at any age, usually occurs as a part of a systemic disorder that involves other mucosal sites, such as the eye (ligneous conjunctivitis), ear, respiratory tract, female genital tract, and kidneys.2 Of the organs affected, gingival tissue is characterized by pseudomembranous, nodular gingival enlargement and periodontal tissue destruction, leading to ligneous gingivitis (LG) and ligneous periodontitis, respectively. Generally, gingival enlargement occurs as a result of a reaction to dental plaque or of exposure to drugs such as phenytoin, cyclosporine, or calcium channel blockers,3 or as part of a systemic syndrome.4 Patients with these conditions have shown marked impairment of wound healing in mucous membranes. Since the major constituent of the pseudomembrane is fibrin(ogen), this raises the possibility of major deficiency ª 2011 Blackwell Publishing Asia Pty Ltd
of (plasmin-mediated) extracellular fibrinolysis in these patients.1 In fact, studies have suggested that hypoplasminogenemia is a common predisposing factor for the development of LG/periodontitis and its associated complications.5–7 We present a rare case of LG associated with plasminogen deficiency and discuss its potential implications. Case report A 66-year-old female presented to the Oral Medicine Clinic at the University of Florida, College of Dentistry (Gainesville, FL, USA) with a chief complaint of constant bleeding, irritation, and soreness of the gums in the molar areas. Her medical history was significant for hypertension treated with lisinopril (Zestril)/hydrochlorothiazide (Hydrodiuril) (20/25 mg/day) and gemfibrozil (Lopid) (600 mg twice a day), peripheral neuropathy treated with gabapentin (Neurontin) (400 mg three times a day), mild arthritis, and glaucoma in her left eye treated with latanoprost ophthalmic solution (Xalatan). She was blind in her right eye as a result of childhood scarring of 207
Pseudomembranous gingiva
the conjunctiva. The patient reported delayed wound healing of skin on her abdomen. On examination, there was no lymphadenopathy or swelling of the neck. The lower lip was erythematous with slight cheilitis, and the tongue was fissured with a scrotal and geographic tongue appearance. The interdental papilla between the right first and second lower molars was ulcerated with significant gingival enlargement and inflammation (Figure 1a). Hypertrophic gum tissue was noted on the upper left molar area (Figure 1b). The gingival tissues on both arches were hypertrophic, especially the maxilla, and exhibited loss of stippling and an uneven hypertrophic surface right above the right upper central incisor (Figure 1c). There was bleeding from the gingival upon palpation. A tentative clinical diagnosis of desquamative gingivitis was made, and the patient underwent an incisional biopsy from the right mandibular buccal gingiva adjacent to the first molar (Figure 1a). Routine microscopic examination revealed inflamed multiple fragments of fibrous tissue surfaced in part by orthokeratinized-stratified squamous epithelium, which exhibited significant thickening of the spinous cell layer with elongated and bulbous rete ridge formation. The most striking feature was replacement of the majority of fibrous connective tissue by the deposition of an amorphous, amyloid-like material (Figure 2a–c). This material contained numerous thin-walled, dilated vascular channels and scattered inflammatory cells. An amyloid stain, namely Congo red, was negative (Figure 2d), while a periodic acid–Schiff stain was positive for the pink material. Antibody staining was granular at the point of the basement membrane (+1 of 4) for C3, and negative for immunoglobulin (Ig)G, IgM, IgA, and fibrinogen. Based on these findings, in combination with the clinical presentation, a diagnosis of LG was rendered. In view of this diagnosis, the patient was referred for a medical work-up. Of significance were the lowered red blood cell count of 3.64 million/lL (reference range: 4.20–5.80 million/lL) and hemoglobin count of 11.4 g/dL (13.2– 17.1 g/dL), increased glucose of 118 mg/dL (65–99 mg/dL) with hemoglobin A1c of 6.2% (
