Ecchymosis and Bullous Lesions on a Young Male’s Back

Pressure bullae, also known as coma bullae, are tense, subepidermal blisters caused by prolonged pressure applied to an area. As such, they are commonly associated with barbiturate overdose and comatose patients. These lesions were first described by Dr. Larrey, Napoleon's...

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Pressure bullae, also known as coma bullae, are tense, subepidermal blisters caused by prolonged pressure applied to an area. As such, they are commonly associated with barbiturate overdose and comatose patients. These lesions were first described by Dr. Larrey, Napoleon’s surgeon in the 19th century. He noted blisters in comatose soldiers after exposure to carbon monoxide.¹ Recently, these lesions have been seen with increasing frequency in the wake of the current opioid epidemic. Cases have recently been published describing patients who overdosed on diazepam, methadone, heroin, carbon monoxide, caffeine, alcohol, and tricyclic antidepressants who subsequently develop pressure bullae after prolonged periods of inactivity.^2,3 Patients with neurologic disorders such as strokes, brain tumors, traumatic brain injuries, spinal cord disease, and encephalitis also frequently have coma bullae. Other associated conditions include chronic renal failure, hyperparathyroidism, and diabetic ketoacidosis, all of which share a common underlying theme of decreased movement and activity.⁴ Overall, the most common risk factor for pressure bullae is prolonged periods of impaired consciousness.

Coma bullae often initially present as erythematous lesions that evolve to become tense bullae or vesicles. The lesions most often develop 2 to 3 days after the onset of altered consciousness or impaired mobility.⁵ The bullae usually resolve on their own in 2 to 4 weeks, either after the patient regains mobility or measures are taken to relieve pressure from the affected area.⁴ Skin biopsies taken from coma bullae reveal subepidermal bullae, epidermal and eccrine sweat gland necrosis with many neutrophils and dermal vessel thrombosis.^5,6 The sweat gland degeneration that is seen in coma blisters has been found to have CD45RO and M30 immunoreactivity. As a result, these immunohistochemical stains can be used to identify sweat gland apoptosis in coma bullae.⁷

Although the exact pathogenesis leading to the formation of coma bullae is unclear, it is known that their development is multifactorial. Hypoxia and tissue ischemia combined with local pressure at the site of the lesion are the most significant contributors to the development of the bullae. This decreased oxygen supply can be seen as a result of arterial hypotension associated with shock, vascular control changes seen in comatose patients, or secondary to the vasoactive changes seen with certain drug ingestions.⁶

The low flow of oxygen to the area leads to necrosis, which most noticeably affects the cells with highest metabolic activity: eccrine sweat glands.⁸ When these damaged areas of skin are subjected to prolonged pressure forces, coma bullae may result. Infection and autoimmune processes are not thought to be involved in pathogenesis, and, surprisingly, reports have argued that frictional forces are unlikely to be involved either as blisters secondary to friction produce intraepidermal rather than subepidermal lesions.² 

Other conditions to consider on the differential diagnosis when coma bullae are suspected are other blistering diseases that may also occur in dependent areas. Bullous disease of diabetes, or bullosis diabeticorum, results in the acute formation of tense, subepidermal bullae, most commonly on the feet or lower legs. These lesions can have diameters extending several centimeters, and histopathologic examination will show intraepidermal and subepidermal blisters.

These lesions also spontaneously resolve during the course of a few weeks. Stasis blisters are another diagnosis to consider, and these form in edematous areas, most commonly on the lower legs. Histologic studies have demonstrated that stasis blisters show epidermal spongiosis and dermal edema. Treating the patient’s edema typically leads to resolution of the blisters. Another etiology to consider on the differential should be bullous leukocytoclastic vasculitis, which presents with subepidermal, hemorrhagic bullae, or vesicles that overlay purpuric plaques.

This cutaneous presentation is due to necrosis of the skin in areas of small vessel vasculitis.⁴ Other conditions to rule out include friction blisters, as well as more unusual cases of bullous disease such as bullous amyloidosis, epidermolysis bullosa, and bullous pemphigoid. 

In establishing a diagnosis of coma bullae, the clinical setting and history alone are oftentimes sufficient to make the diagnosis. However, histologic findings of subepidermal bullae and necrosis of eccrine sweat glands can also confirm the diagnosis. In nondrug-induced coma blisters, the most frequent histologic finding is the lack of epidermal inflammation and the presence of vessel thrombosis in the dermis.⁹ 

Treatment of this condition includes mobilizing the patient and relieving pressure. Wound care to prevent infection is recommended, including sterile drainage, maintaining the overlying skin flap to cover most of the lesion, and hydrocolloid dressings.¹⁰ If these treatments are pursued promptly, the lesions typically resolve in 2 to 4 weeks. Systemic complications are rare if pressure is eliminated and proper wound care is followed. 

The 20-year old patient in this case was rotated from side to side and given a pressure relief cushion to lay on until he could ambulate. The patient’s bullae resolved after about 3 weeks with supportive care and ambulation. 

Michelle Lee, BA, is a medical student, Joan Fernandez, BS, is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

References

1. Ruiz‐Rivero J, Pulido‐Pérez A, Suárez‐Fernández RM. Coma blisters with deep soft tissue involvement after drug overdose. Int J Dermatol. 2017;56:881-883.
2. Herschthal D, Robinson MJ. Blisters of the skin in coma induced by amitriptyline and clorazepate dipotassium: Report of a case with underlying sweat gland necrosis. Arch Dermatol. 1979;115:499-499.
3. Arndt KA, Mihm MC, Jr, Parrish JA. Bullae: a cutaneous sign of a variety of neurologic diseases. J Invest Dermatol. 1973;60:312-320.
4. Sami N, Yeh SW, Ahmed AR. Blistering diseases in the elderly: diagnosis and treatment. Dermatol Clin. 2004;22:73-86.
5. Bosco L, Schena D, Colato C, Biban P, Girolomoni G. Coma blisters in children: case report and review of the literature. J Child Neurol. 2013;28:1677-1680.
6. Chacon AH, Farooq U, Choudhary S, et al. Coma blisters in two postoperative patients. Am J Dermatopathol. 2013;35:381-384.
7. Kashiwagi M, Ishigami A, Hara K, et al. Immunohistochemical investigation of the coma blister and its pathogenesis. J Med Invest. 2013;60:256-261.
8. Rocha J, Pereira T, Ventura F, Pardal F, Brito C. Coma Blisters. Case Rep Dermatol. 2009;1:66-70.
9. Kato N, Ueno H, Mimura M. Histopathology of cutaneous changes in non-drug-induced coma. Am J Dermatopathol. 1996;18:344-350.
10. Arndt KA. Coma blister (comma bullae, drug-induced coma blisters, barbiturate blisters, neurologic blisters). 2017. Available at: https://www.clinicaladvisor.com/dermatology/coma-blister-comma-bullae-drug-induced-coma-blisters-barbiturate-blisters-neurologic-blisters/article/593874/ (Accessed May 7, 2018).