DR [Dermatology Reports 2014; 6:5282] [page 5] Angina bullosa hemorrhagica: report of 11 cases Julieta Ruiz Beguerie,1 Silvina Gonzalez2 1Dermatology Department, Austral University Hospital, Austral University, Buenos Aires; 2Dermatology Department, Stomatology Clinic, Hospital de Clinicas Jose de San Martin, Buenos Aires, Argentina Abstract Angina bullosa hemorrhagica is a rare and benign disorder, usually localized in the subep- ithelial layer of the oral, pharyngeal and esophageal mucosa. The lesions are character- ized by their sudden onset. They appear as a painless, tense, dark red and blood-filled blis- ter in the mouth that rapidly expand and rup- ture spontaneously in 24-48 hours. The under- lying etiopathology remains ill defined, although it may be a multifactorial phenome- non including diabetes, and steroid inhalers. The condition is not attributable to blood dyscrasias, nor other vesicular-bullous disor- ders. In this study, eleven patients with such blisters are described. Physical examination of the patients revealed a single blister with hem- orrhagic content localized in the oral mucosa. Biopsy of the lesions showed sub epithelial blisters with a mild infiltrate. In general prac- tice, dermatologists could face a blood-filled bullous lesion of the oral mucosa. Recognition is, therefore, of great importance for dermatol- ogists. Introduction In 1967 Badham was the first to introduce the term angina bullosa hemorrhagica (ABH), a bullous disorder in which recurrent oral blood blisters appear in the absence of any identifiable systemic disorder, which heal uneventfully within 1 week.1,2 Other names that have been given to this disorder are benign hemorrhagic bullous stomatitis and recurrent or traumatic oral hemophlycteno- sis.3,4 It can be one or more blood-filled blisters occurring at the same time and it is usually not painful, occurring in adults between 50-70 years old. There is no strong predilection for either male or female. They all heal sponta- neously without scarring.4,5 Case Report We studied 11 patients (4 males and 7 females) with ABH. The mean age was 65 (range 46-86 years). All cases presented with a similar history of a single, localized blood-filled blister, which measured 4 to 7 mm in diameter (Figure 1). The blister spontaneously burst in 2-4 days, leaving a hemorrhagic content flow and erosion for 7 to 10 days. On examination, the Nikolsky sign was negative. Recurrences were seen in 2 patients. Eight of the 11 patients had the blister localized to the palate. The remaining three subjects had one lesion each localized to the lateral anterior third of the tongue, the gums and the jugal mucosa (Figure 2). Sixty four percent (7/11) had an associated systemic disease at the time of their initial visit. Four of these 7 individuals had arterial hypertension and 2 others had well-controlled NIDDM (non-insulin depend- ent DM) (Table 1). Trauma by sharp edges of adjacent teeth and metal crowns were identi- fied as etiological factors in 4 cases. Lesions healed after removal of the metal crown and rounding of the sharp-edged teeth. Patients did not report a tendency to bleed at other sites. Laboratory evaluation failed to disclose any underlying illness. Platelet counts and coagulation tests were within normal limits in all patients. The histopathology report in all cases reported a sub epithelial bulla filled with blood. Additionally there was an underlying mild to moderate nonspecific mononuclear inflamma- tory cell infiltrate, which was generally limited to the region of the lamina propria. Occasionally, neutrophils were seen. Performing a biopsy of an intact bulla is diffi- cult because of the short duration in which the lesion stays intact (24-72 hours). Otherwise, a biopsy of a ruptured bulla only exhibits a non- specific ulceration. Direct immunostaining for immunoglobulin G, A, or C3 are consistently noncontributory. These patients were safely monitored with regular follow-ups due to minimal risk of com- plications. Discussion ABH presents clinically with blood-filled blisters that occur predominantly on the soft palate. They generally reach a diameter of 2±3 cm.6 They tend to burst spontaneously, leaving a ragged ulcer that heals without scarring. Approximately 30% of patients may have a recurrence.4 Occasionally patients may present clinically with hoarseness, or even blood-tinged sialor- rhea. Following the rupture of the blister, painful ulcers may be present. The incidence is similar in both sexes (women, 52%; men, 48%).4 Laboratory evaluation, including CBC and coagulation profile, usually fails to dis- close an underlying illness. Its etiology remains obscure. ABH has been associated with a constitutional predisposi- tion, such as loose cohesion between the epithelium and the corium of the mucosa, or a weak anchorage of mucosal vessels. This may predispose to sub-epithelial hemorrhages. As potential etiological factors, it has also been linked to arterial hypertension, diabetes melli- tus and the long-term use of inhaled steroids.4,7,8 Grinspan et al., noted an associa- tion with diabetes mellitus, hyperglycemia, and/or a family history of diabetes in 44.4% of the 54 cases they studied with ABH.4 Stephenson published a large series of 30 patients, not finding a clear precipitating fac- tor in 47% of the cases.6 There have been many precipitating factors described: trauma by a sharp cusp or edge of an adjacent tooth or metal crown, masticatory trauma, hot drinks, use of steroids, as well as dental or anesthetic procedures.6,9,10 The differential diagnosis is broad, includ- ing pemphigus, mucosal pemphigoid, cicatri- cial pemphigoid, epidermolysis bullosa acquisita, linear IgA dermatosis, toxidermia, bullous lichen planus, erythema multiforme, oral amyloidosis and fixed drug eruption. Haemorrhagic blisters can also appear in the setting of leukemia, vasculitis and other haematological and haemostatic disorders.11 Dermatology Reports 2014; volume 6:5282 Correspondence: Julieta Ruiz Beguerie, Dermatology Department, Austral University Hospital, Av. Juan Domingo Perón 1500, Buenos Aires 1629, Argentina. Tel.: +54.1230.448.2000 E-mail: jruiz@cas.austral.edu.ar Key words: angina bullosa haemorrhagica, bul- lous hemorrhagica, oral mucosa blisters. Contributions: the authors contributed equally. Conflict of interests: the authors declare no potential conflict of interests. Received for publication: 2 January 2014. Revision received: 6 February 2014. Accepted for publication: 15 March 2014. This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY- NC 3.0). ©Copyright J.R.Beguerie and S.Gonzalez, 2014 Licensee PAGEPress, Italy Dermatology Reports 2014; 6:5282 doi:10.4081/dr.2014.5282 No n- co mm er cia l u se on ly [page 6] [Dermatology Reports 2014; 6:5282] The histopathology reveals haemorrhagic subepithelial bullae, non-specific ulceration and a chronic inflammatory cell infiltrate in the lamina propria.6 In 1990, Edward was the first to document a case of an intradermal blis- ter. This had not been described previously in the literature.9 Direct immunofluorescence is usually nega- tive, but equivocal immunostaining for IgG and C3 has been previously reported.6,12 Although the risk of asphyxia is probably remote, palatal or pharyngeal blisters should be ruptured in order to prevent upper airway obstruction. In rare occasions, the size of the bulla and the free blood in the larynx requires intubation of the trachea by either fibreoptic endoscopy or direct laryngoscopy, or securing the airway by surgical tracheostomy.12 Treatment is symptomatic. Lesions can be treated successfully with topical steroids. Some lesions may heal after removal of the metal crown and rounding of the cusp prevent- ing constant trauma.13-16 Conclusions The aim of this paper is to report the clinical features and describe the management of 11 cases of ABH. We feel it is extremely important to distinguish this benign disorder from other more serious blistering diseases of the oral mucosa with similar presenting features. This disorder is likely under-reported. The lack of knowledge of this entity makes it very likely to be under-diagnosed. The recognition of the lesion is of great importance to avoid misdiagnosis. The examination of the oral mucosa and the skin, together with the med- ical history are the keys to diagnosis. The prog- nosis is good and this should also be stressed when advising patients. In general practice, the dermatologist can be confronted with a blood-filled bullous lesion of the oral mucosa. Recognition is, therefore, of great importance for dermatologists. Case Report Table 1. Characteristics of the patients with angina bullosa haemorrhagica. Patient Age Gender Associated disease Location 1 73 F HTN Palate 2 86 F HTN Palate 3 65 M DBT, MI Palate 4 57 M - Palate 5 46 F - Palate 6 66 F Colon cancer Palate 7 70 F Prostate cancer Palate 8 63 M Alcoholism Palate 9 48 M - Gums 10 84 F HTN, breast cancer Tongue 11 52 F - Jugal mucosa HTN, hypertension; MI, myocardial infarction; DBT, diabetes. Figure 1. Single localized blood-filled blister of the oral mucosa (case 1). Figure 2. Blister in oral mucosa (other cases). 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