Heparin-Induced Bullous Hemorrhagic Dermatosis Confined to the Oral Mucosa

Comment

Heparin-Induced Skin Lesions
The 2 most common types of heparin-induced skin lesions are delayed-type hypersensitivity reactions and immune-mediated HIT. A 2009 Canadian study found that the overwhelming majority of heparin-induced skin lesions are due to delayed-type hypersensitivity reactions.⁴ The majority of these reactions occurred at or near the injection site on the abdomen and presented as eczematous plaques. Distant cutaneous involvement and lesions of the buccal mucosa were not as commonly reported. Female sex, obesity, and heparin treatment exceeding 9 days were identified as risk factors in the development of delayed-type hypersensitivity reactions, but our patient did not have any of these risk factors.⁴

Types of HIT
Heparin-induced thrombocytopenia is one of the most serious adverse reactions to heparin administration. There are 2 subtypes of HIT, which differ in their clinical significance and pathophysiology.⁹ Type I HIT is a non–immune-mediated reaction that results from the direct effect of heparin on platelets, which causes platelet aggregation and thrombocytopenia. It presents within the first 2 days after heparin exposure.

Type II HIT is an immune-mediated response caused by the formation of IgG autoantibodies against the heparin–platelet factor 4 complex. Antibody formation and thrombocytopenia typically occur after 4 to 10 days of heparin exposure, and there can be devastating arterial and venous thrombotic complications.

Diagnosis of HIT
Heparin-induced thrombocytopenia should be suspected in patients with a lowered platelet count, particularly if the decrease is more than 50% from baseline, and in patients who develop stroke, MI, pulmonary embolism, or deep vein thrombosis while on heparin. Heparin-induced thrombocytopenia was not observed in our patient, as his platelet count remained stable between 160,000 and 164,000/µL throughout his hospital stay and he did not develop any evidence of thrombosis.

Differential Diagnosis
Our patient’s lesions appeared morphologically similar to angina bullosa haemorrhagica, but this condition was less likely based on other clinical features. Typically, angina bullosa haemorrhagica appears as a solitary, blood-filled blister due to oral mucosal trauma from the ingestion of hard or abrasive food.¹⁰ Angina bullosa haemorrhagica most often is located on the soft palate because of its susceptibility to injury during mastication, and this lesion tends to be painful.¹¹ In contrast, our patient developed 7 painless lesions on the buccal mucosa, sparing the soft palate, and without any history of preceding trauma.

Bullous pemphigoid also was considered given the presence of tense bullae in an elderly patient. However, the rapid and spontaneous resolution of these lesions with complete lack of skin involvement made this diagnosis less likely.¹²

Heparin-Induced Bullous Hemorrhagic Dermatosis
Because our patient described a similar reaction while taking enoxaparin in the past, this case represents an idiosyncratic drug reaction, possibly from antibodies to a heparin-antigen complex. Heparin-induced bullous hemorrhagic dermatosis is a rarely reported condition with the majority of lesions presenting on the extremities.

Conclusion

We describe a rare side effect of heparin therapy characterized by discrete blisters on the oral mucosa. However, familiarity with the spectrum of reactions to heparin allowed the patient to continue heparin therapy despite this side effect, as the eruption was not life-threatening and the benefit of continuing heparin outweighed this adverse effect.