At least 30 percent of patients with diabetes will develop cutaneous manifestations in their lifetime.1 Given that diabetes is a systemic disease, its effects on the skin may arise from many different sources (vascular, metabolic, nutritional disturbances, infectious agents and medications). Several common skin disorders may be associated with diabetes. These include necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic bullae, diabetic dermopathy, limited joint mobility and yellow skin phenomenon.
While the exact causes of most pathologic skin changes are unknown, a majority of the skin changes associated with diabetes are related to similar skin changes found with microvascular disorders.
Taking A Closer Look At Necrobiosis Lipoidica Diabeticorum
Necrobiosis lipoidica diabeticorum (NLD) is probably the most well known of skin disorders strongly associated with diabetes mellitus. Muller and his colleagues at the Mayo Clinic found frank diabetes, related biochemical changes, glucose intolerance or positive family history in 90 percent of presenting cases.1 In 15 percent of those cases, the appearance of NLD preceded the diagnosis of diabetes by one to five years. When you see NLD, you should suspect underlying diabetes.
NLD is a rare condition that manifests in only 0.3 percent of the diabetic patient population although it affects females four times as much as males. Also keep in mind that NLD appears earlier in life (30 years) in the diabetic population than in the non-diabetic population (41 years).2
Early presentation of NLD varies from erythematous to violaceous papules or plaques with or without scaling. As the lesions progress, they become increasingly atrophic and assume the characteristic atrophic, waxy, yellow, telangiectatic appearance. These lesions are commonly multiple, bilateral and almost involve the pretibial regions of the lower extremity in 85 percent of the cases. You may also see these lesions on the scalp, arms, trunk, and face. Be aware that common differential diagnoses include: Granuloma annulare, rheumatoid nodule and sarcoidosis.
Light microscopy studies have implicated microvascular disease as an underlying etiology for NLD lesions. However, in up to 30 percent of cases, there is no evidence of vascular disease and researchers have proposed numerous other etiologies including immunopathy, dyslipidemia, abnormal collagen function and vasculopathy. No one mechanism has been satisfactory, although trauma does seem to play a role.2
Typically, one third of lesions ulcerate and only 10 to 20 percent resolve after 10 years.3 Most lesions evolve into the classic atrophic, waxy, yellow lesions that are predisposed to ulceration. Up to 30 percent of these progress on to ischemia, gangrene and ultimately ulceration incited by minor trauma or tissue stress.
Treatment Tips For NLD
No correlation has been found between progression of NLD lesions and glucose control. You may treat early raised lesions with injectible steroids into the advancing border. When it comes to older flat lesions, you should use topical steroids. Recently, researchers have reported some success in using anti-platelet therapy, but the potential role of this therapy awaits further studies.4
It’s important to protect the pretibial areas from trauma in order to prevent ulceration of these sensitive lesions. If the lesions have ulcerated, you should treat them with appropriate wound care therapy including local debridement, topical or systemic antibiosis and grafts when indicated.
Key Insights On Granuloma Annulare
In contrast, granuloma annulare is a relatively common skin disorder and not considered to be a marker for diabetes. Only 21 percent of patients with granuloma annulare have diabetes.5 This skin disorder has striking similarities to NLD and may appear as a generalized or localized disorder. Eighty-five percent of cases are localized. This is a self-limiting process that generally resolves in several years. The average age of onset is 51 years.
Lesions begin as dermal papules and gradually expand into annular borders with central hyperpigmentation. These may appear in the hundreds and may coalesce into annular plaques. The dorsum of the hands and arm are the most common sites with the feet and legs less frequently involved.
The pathophysiology of this disease is unknown. Trauma, infectious processes, genetic disposition, vasculitis and sun exposure have all been suggested as causes without convincing corroborative evidence. Histologically, there is a normal epidermal layer with underlying granulomatous and necrotic upper dermis. These lesions are benign and tend to heal spontaneously without scarring. If you feel treatment is necessary, you may use topical or intralesional steroids.
What About Diabetic Dermopathy And Diabetic Bullae?
Diabetic dermopathy was extensively studied first by Melin in 1964 and was later termed diabetic dermopathy by Binkley one year later.5 Binkley used the term diabetic dermopathy because he believed that the appearance of this entity was diagnostic for diabetes. This is now known to be untrue yet people still use the name. The incidence of this entity is estimated at 30 to 60 percent of diabetic patients with an incidence of 20 percent in non-diabetic patients for age-matched controls.6 The incidence of diabetic dermopathy appears to be greatest in patients with diabetic neuropathy with a male predominance of two to one.7
These lesions are generally asymptomatic and begin as pink patches approximately 0.5-1.0 cm in diameter. Over the next few weeks, these lesions evolve into brown, hyperpigmented, atrophic patches. Individual lesions generally resolve over the course of two years but are continually replaced by new ones. These lesions may heal with or without atrophy and/or hyperpigmentation. They do not require treatment.
The etiology is unknown but is believed to be related to trauma. It was found that diabetic patients with diabetic dermopathy subjected to heat trauma developed additional lesions. However, patients without diabetic dermopathy did not develop lesions.8 Prognosis of lesions is independent of glucose control.
An extremely rare manifestation of longstanding diabetes, diabetic bullae appear in the distal extremeties. Tense blisters form sponatenously without incidence of trauma usually on the feet and shins.9 Blisters are generally non-inflammatory, asymptomatic and rapidly evolving. These blisters generally heal without scarring in several weeks but recurrence may be expected. You may treat bullae topically with local wound care.
Other Pertinent Pointers On Skin Disorders
The findings of thick, tight, waxy skin have been prevalent in diabetics. The thickened, waxy skin limits movement in joints. Up to 50 percent of patients who have had diabetes for 4.5 years or longer were found to have joint limitation.
This is most easily demonstrated by the inability of patients to approximate the palmar surfaces of the proximal and distal interphalangeal joints. This has also been called the “prayer sign.”
The diminished mobility of the skin is related to increased cross-linking and abnormal collagen metabolism. The development of limited joint mobility may lead to an increased risk of microvascular disease as evidenced by nephropathy, retinopathy and neuropathy.10
Yellowing of the palms, soles and face occurs in as many as 10 percent of patients with diabetes. This yellow discoloration is similar to that seen in excess carotene intact. However, this does not seem to be the cause in patients with diabetes. Carotene levels appear normal in the skin of diabetic patients. The cause of this yellow discoloration is unknown. This condition is harmless and never seen in the conjunctiva, thus differentiating this pigmentation from jaundice.
There are many manifestations of diabetes in the skin, yet there is little information on the pathophysiology of the skin disorders discussed above. Exactly why do these disorders have greater incidence in the diabetic population? In the coming years, perhaps a common thread in the pathology of these disorders may be found and more effective treatments may be elicited.
For now, being able to recognize the skin manifestations and their natural history will allow us to educate patients and select appropriate treatment courses.
Dr. Yung is a first-year resident at the University of Texas Health Science Center in San Antonio.
Dr. Steinberg (pictured) is an Assistant Professor in the Department of Orthopaedics/Podiatry Service at the University of Texas Health Science Center.
1. Muller SA, Winkelmann RK: Dermatologic disorders associated with diabetes mellitus. Mayo Clin Proc 41:689-703, 1966.
2. Lowitt, MH and Dover, JS. Necrobiosis Lipoidica. J. Am Acad Dermatol, 1992, 25:735-748.
3. Muller SA, Winkelmann RK Necrobiosis Lipoidica: Histopathologic study of 98 cases. Arch Dermatol. 1966 94:1-10.
4. Tkach JR. Platlet-inhibitiaon therapy of ulcerated necrobiosis lipoidica diabeticorum. Dermatol Allergy 5:9-12, 1982.
5. Allen GE, Diabetes mellitus and the Skin. Practitioner 203: 189, 1969.
6. Bauer M and Levan NE, Diabetic dermangiopathy. A spectrum including pretibial pigmented patches and necrobiosis lipoidca diabeticorum. Br J Dermatol, 1970. 83:528-535.
7. Aagenaes O, Moe H. Light and electron microscopy study of skin capillaries of diabetics. Diabetes 1961 10: 253-259.
8. Lithner F. Cutaneous reactions of the extremities of diabetic to local thermal trauma. Acta Med Scand, 1975. 198: 319-325.
9. Bodman M, Frideman S and Clifford L. Bullosis diabeticorum. A report of two cases with a review of the literature. JAPMA 1991 81: 561-563.
10. Rosenbloom AL, Silverstien JH, Lezotte D, et. al. Limited Joint Mobility in Childhood Diabetes Mellitus Indicates Increased Risk For Microvascular Disease NEJM 305: 191-194.