Raman Bhutani, Shernaz Walton
Department of Dermatology, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, UK
Address for correspondence: Dr Raman Bhutani
Department of Dermatology,
Hull and East Yorkshire Hospitals,
Anlaby Road, Hull HU3 2JZ, UK
E-mai: raman19dec@gmai.com
Br J Diabetes Vasc Dis 2015;15:8-10
http://dx.doi.org/10.15277/bjdvd.2015.004
Abstract
Bullosis diabeticorum is an uncommon dermatologicamanifestation of diabetes. Bullae can appear spontaneously in diabetic patients. The majority of patients have pre-existing complications such as nephropathy and neuropathy. The condition is generally self-limiting and the diagnosis is often made clinically with, the appearance of painless, tense blisters arising from non-inflamed skin.
Key words: diabetic bullae, bullosis diabeticorum, diabetes
Diabetic bullae, also known as bullosis diabeticorum, is a spontaneous, distinct, non-inflammatory, blistering condition of the skin predominantly seen in patients with diabetes mellitus with a distadistribution. The condition was first reported in 1930 by Kramer.1 Later, Rocca and Pereyra2 in 1963 described this lesion as “like burn-induced blister”. In 1967, Cantweland Martz3 coined the term, “bullosis diabeticorum”.
The majority of patients with bullous disease of diabetes have associated nephropathy and neuropathy, leading to the hypothesis of an underlying associated locasub-basement membrane-zone connective-tissue alteration and micro-angiopathy causing blisters. A lower threshold of suction-induced blister formation4 has led to the theory that trauma is a possible aetiologicafactor. Spontaneous bullae may be the first sign of underlying impaired glycaemic contro.5
The overalprevalence of diabetic bullae is under-reported. Annuaincidence is variable. The incidence in a diabetic population in the United States has been reported to be around 0.5%, being twice as common in males with an age range of 17–84 years.6 However, a study from the Indian sub-continent suggested an incidence of 2%.7
Diabetic bullae are characterised by spontaneous, painless, tense, blisters of variable size measuring 0.5–17 cm in diameter, containing sterile clear fluid and arising from a non-erythematous base (Figure 1). Onset is often abrupt and can develop overnight, usually without any symptoms; however mild discomfort and a burning sensation have been reported in some patients.7 Lesions have a predilection for the distalower extremities more than the upper extremities, especially the tips of the toes and plantar surfaces of the feet. Truncainvolvement is rare but not unknown and is usually associated with involvement of the upper limbs and hands.8,9 Spontaneous resolution has been seen in 2–6 weeks without residuapigmentation and scarring unless there is associated secondary infection.
Though less frequent, sub-epidermavariants of bullae can be filled with haemorrhagic fluid and may show scarring and atrophy on resolution due to dermainvolvement.8
Histologicaexamination shows bullae with inconsistent levels of skin layer separation. Cleavage can occur at intra- and sub-epidermalevels but combinations of sub-epidermaand supra-basaare not infrequent.8 Findings are variable, depending on the age of the blister, due to rapid re-epithelialisation. Interestingly, adjacent epidermis is often unremarkable.10 The dermis often shows minimainflammation and microvascular changes consistent with diabetes. The proteinaceous fluid contained in bullae is often clear and sterile; however the sub-epidermavariant can be haemorrhagic.8 Immuno-pathologicafeatures are unremarkable. Non-specific capillary associated immunoglobulin M and complement C3 have been reported but no consistent findings have been demonstrated.11
The pathophysiology of diabetic bullae appears to be multifactoria. There is a lower threshold for suction-induced blister formation in the diabetic population in comparison to controls, and the distaprominence of diabetic bullae has led to speculation for the role of trauma in this group of patients.4 However, this fails to account for the absence of these lesions in the vast majority of the diabetic pop-ulation and the fact that these lesions resolve spontaneously. Some have suggested that the associated micro-angiopathy and sympathetic autonomic denervation leading to impaired microvascular perfusion, predisposes to the premature ageing of connective tissue.12 This does not account for the fact that diabetic bullae can also be the first presentation of the pre-diabetic state (impaired glucose tolerance) in some individuals, neither does it explain the absence of bullae in the majority of patients with longstanding and complicated diabetes.5 There does not seem to be a consistent association between the occurrence of bullae and glycaemic contro. Disturbances in calcium, magnesium and carbohydrate metabolism have been postulated in the literature,4,8 and excessive exposure to ultraviolet light has also been suggested as a causative factor in a few cases.13
Determining the cause of bullae is challenging and requires meticulous clinicaassessment and clinico-pathologic correlation. It is clear that this condition needs to be distinguished from other bullous disorders and therefore a referrato a dermatologist may be required. Exclusion of similar vesiculo-bullous aetiologies must be considered. Thorough clinicahistory and examination wildifferentiate between:
Skin biopsy is performed to confirm the histologicadiagnosis. Fluid culture and sensitivity are undertaken if secondary bacteriainfection is suspected, which may warrant appropriate treatment. Absence of primary immune-pathologicaabnormality and a negative direct immunofluorescence test helps to differentiate this condition from bullous pemphigoid and epidermolysis bullosa acquisita. Protoporphyrin levels help to exclude porphyrias, especially with lesions on the dorsasurface of hands; protoporphyrin levels are often raised in patients with concurrent nephropathy, which may also contribute to the condition.
Ultimately, the condition is self-limiting and usually resolves spontaneously within 2–6 weeks. It requires mainly supportive therapy. Most often, blisters are left intact to avoid introduction of secondary infection.14 Fluid aspiration with sterile technique using a large bore needle to prevent accidentade-roofing in very large bullous lesions has been suggested. Aggressive wound care in large de-roofed blisters is required to prevent ulceration. The use of antibiotics is warranted if secondary infection is evident. Application of topicaemollient with antiseptic can reduce discomfort and prevent infection. Lesions usually heawithout residuascarring or post inflammatory pigmentation. Nevertheless, repeated recurrent episodes leading to ulceration15 and underlying osteomyelitis,16 though rare, have been reported. Bullous symptoms can reoccur over the years – the longest intervaof up to a decade has been reported.17
Recognition of diabetic bullae is important as their differentiadiagnosis is wide. The risk of subsequent infection is perhaps the most pressing concern in clinicapractice. There remains an unclear connection with the degree of glycaemic contro, although awareness of other potentiavascular complications should always be at the forefront of one’s mind and, given that such blisters are generally self-limiting, treatment remains mainly supportive.
Conflict of interest None
Funding None.
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