A 26-year-old male presented with a 5-year history of blood-filled blisters of the oral mucosa. He intermittently developed pea- to quarter-sized bullae on his buccal cheek, tongue, soft palate (Fig 1, A and B), hard palate (Fig 1, C), and/or uvula (Fig 1, D). The bullae filled rapidly with blood before spontaneously rupturing to form erosions. After rupturing, the bullae healed without scarring within 5 to 7 days. He had previously undergone a biopsy from the palate (Fig 2), which showed an ulcerated mucosal surface with negative direct immunofluorescence (DIF). The patient also reported easy bruising, especially when playing contact sports, but denied blisters on other areas of his body, hypermobility, and personal or family history of skin disease or bleeding disorders.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: What is the most likely diagnosis given this patient’s clinical presentation?A.Bullous pemphigoid (BP)B.Oral lichen planusC.Epidermolysis bullosa acquisitaD.Angina bullosa hemorrhagica (ABH)E.Pemphigus vulgaris Answers:A.Bullous pemphigoid (BP) – Incorrect. Although 10% to 20% of patients with BP can have mucosal involvement, isolated mucosal BP is uncommon. Histologically, BP is characterized by subepidermal blister formation with abundant eosinophils on hematoxylin and eosin (H&E) stain as well as linear deposition of IgG and C3 along the basement membrane zone on DIF.B.Oral lichen planus – Incorrect. Oral lichen planus typically presents with white, reticular, lacy plaques rather than hemorrhagic bullae. The disease predominantly affects the gingiva, labial, and buccal mucosae. Involvement of the palate is uncommon. H&E is notable for irregular acanthosis of the epidermis as well as dense band like lymphocytic inflammation along the dermal epidermal junction. Shaggy fibrin deposition along the dermal epidermal junction may be seen on DIF.C.Epidermolysis bullosa acquisita – Incorrect. While epidermolysis bullosa acquisita can have oral mucosal involvement, histology is typically notable for a subepidermal blister with mixed inflammation on H&E as well as a linear deposition of IgG along the cutaneous basement membrane zone on DIF, similar to that seen in BP.D.Angina bullosa hemorrhagica (ABH) – Correct. ABH is a poorly understood condition characterized by recurrent, short-lived, hemorrhagic bullae located on the mucous membrane lining the oral cavity.1Ordioni U. Hadj Saïd M. Thiery G. Campana F. Catherine J.H. Lan R. Angina bullosa haemorrhagica: a systematic review and proposal for diagnostic criteria.Int J Oral Maxillofac Surg. 2019; 48: 28-39https://doi.org/10.1016/j.ijom.2018.06.015Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar The bullae rapidly expand and then spontaneously rupture and heal without scarring or discomfort. Histologic findings in ruptured lesions show epidermal erosions. In this case, H&E stained sections reveal a submucosal bulla with denuded but otherwise unremarkable mucosa (Fig 2, A and B). The dermis is notable for marked papillary edema with a mixed inflammatory infiltrate consisting predominantly of lymphocytes and scattered neutrophils. (Fig 2, C and D). No vasculitis or intraepidermal separation is identified, and DIF studies are negative.E.Pemphigus vulgaris – Incorrect. While pemphigus vulgaris can have mucosal involvement, it is typically characterized by intraepidermal blisters on H&E as well as deposition of IgG in the epidermis between the keratinocytes in a net-like pattern on DIF. Question 2: Which of the following is not in the proposed diagnostic criteria for this condition?A.Exclusively oral or oropharyngeal localizationB.Spontaneous resolution without scarringC.Negative DIFD.Family history of similar symptomsE.Normal platelet count and coagulation studies Answers:A.Exclusively oral or oropharyngeal localization – Incorrect. Diagnostic criteria for ABH were proposed by Ordioni et al1Ordioni U. Hadj Saïd M. Thiery G. Campana F. Catherine J.H. Lan R. Angina bullosa haemorrhagica: a systematic review and proposal for diagnostic criteria.Int J Oral Maxillofac Surg. 2019; 48: 28-39https://doi.org/10.1016/j.ijom.2018.06.015Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar in 2019 (listed below). According to their proposal, meeting 6 of the 9 criteria, including criteria 1 (clinically visible hemorrhagic bullae with a history of bleeding) and criteria 2 (exclusively oral or oropharyngeal localization) are sufficient for a diagnosis of ABH. In this case, the patient met all 9 criteria and had a very classical presentation of ABH, including well-defined, blood-filled blisters in the oral cavity, which rapidly expanded before spontaneously rupturing and healing.Diagnostic criteria for ABH proposed by Ordioni et al1Ordioni U. Hadj Saïd M. Thiery G. Campana F. Catherine J.H. Lan R. Angina bullosa haemorrhagica: a systematic review and proposal for diagnostic criteria.Int J Oral Maxillofac Surg. 2019; 48: 28-39https://doi.org/10.1016/j.ijom.2018.06.015Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar meeting a total of 6 criteria (including criteria 1 and 2) are sufficient for a diagnosis of ABH.1.Clinically visible hemorrhagic bullae with a history of bleeding2.Exclusively oral or oropharyngeal localization3.Palate localization4.Triggering event or promoting factors (eg, trauma, mastication)5.Recurrent lesions6.Spontaneous resolution without scarring within a few days7.Lesions are either painless or associated with a tingling or burning sensation8.Normal platelet count and coagulation studies9.Negative direct immunofluorescenceB.Spontaneous resolution without scarring – Incorrect. Spontaneous resolution without scarring is part of the proposed diagnostic criteria for ABH.C.Negative DIF – Incorrect. Negative direct immunofluorescence is part of the proposed diagnostic criteria for ABH as it helps rule out autoimmune blistering diseases, including BP and pemphigus vulgaris.D.Family history of similar symptoms – Correct. Ordioni et al1Ordioni U. Hadj Saïd M. Thiery G. Campana F. Catherine J.H. Lan R. Angina bullosa haemorrhagica: a systematic review and proposal for diagnostic criteria.Int J Oral Maxillofac Surg. 2019; 48: 28-39https://doi.org/10.1016/j.ijom.2018.06.015Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar conducted a systematic review and found 225 cases of ABH published between 1985 and 2016. Only 8% of patients in this cohort had a family history of ABH. Thus, a family history of similar symptoms is not part of the proposed diagnostic criteria for ABH.E.Normal platelet count and coagulation studies – Incorrect. Normal platelet count and coagulation studies is part of the proposed diagnostic criteria for ABH. Question 3: What is the best next step in management of this patient?A.Benzydamine hydrochloride sprayB.Chlorhexidine gluconate mouthwashC.Incision and drainageD.Expectant management and trauma avoidanceE.Ascorbic acid supplementation Answers:A.Benzydamine hydrochloride spray – Incorrect. Benzydamine hydrochloride spray has been employed in the treatment of ABH to reduce discomfort.2Gibson J. Oropharyngeal blood blisters are known as angina bullosa haemorrhagica.BMJ. 1997; 314: 1625https://doi.org/10.1136/bmj.314.7094.1625Crossref PubMed Google Scholar However, expectant management is first-line management in patients with small lesions that do not impact daily functioning to a significant degree.B.Chlorhexidine gluconate mouthwash – Incorrect. Chlorhexidine gluconate mouthwash has been employed in the treatment of ABH to prevent secondary infection.3Grinspan D. Abulafia J. Lanfranchi H. Dds Angina bullosa hemorrhagica.Int J Dermatol. 1999; 38: 525-528https://doi.org/10.1046/j.1365-4362.1999.00682.xCrossref PubMed Scopus (30) Google Scholar However, expectant management is first-line management in patients with small lesions that do not impact daily functioning to a significant degree.C.Incision and drainage – Incorrect. A potential major risk of ABH are large bulla that can obstruct the airway. For particularly large bulla, incision and drainage may be required to limit its size and progression.4Prabhakar Shashikala R. Angina bullosa haemorrhagica rare cause of upper airway obstruction.Emerg Med J. 2015; 32: 238https://doi.org/10.1136/emermed-2014-203848Crossref PubMed Scopus (6) Google ScholarD.Expectant management and trauma avoidance – Correct. While the pathogenesis of ABH is still largely unclear, mucosal trauma (via mastication, procedures, or other local trauma) seems to be a major provoking factor and described in up to 76% of cases.1Ordioni U. Hadj Saïd M. Thiery G. Campana F. Catherine J.H. Lan R. Angina bullosa haemorrhagica: a systematic review and proposal for diagnostic criteria.Int J Oral Maxillofac Surg. 2019; 48: 28-39https://doi.org/10.1016/j.ijom.2018.06.015Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar As such, treatment of ABH focuses on avoidance of oral trauma, including sharp or coarse food, hot or spicy food, and unnecessary dental procedures.E.Ascorbic acid supplementation – Incorrect. Ascorbic acid 200 mg twice daily has been employed in the treatment of ABH to help avoid recurrences.3Grinspan D. Abulafia J. Lanfranchi H. Dds Angina bullosa hemorrhagica.Int J Dermatol. 1999; 38: 525-528https://doi.org/10.1046/j.1365-4362.1999.00682.xCrossref PubMed Scopus (30) Google Scholar However, expectant management is first-line management in patients with small lesions that do not impact daily functioning to a significant degree. None disclosed.