Dermatologic manifestations of diabetes mellitusRohan Gunathilake MDJohn Hunter Hospital, Newcastle, Australia

Dermatologic manifestations of diabetes• Incidence 30-70% of diabetics in different studies• May precede development of clinical diabetes• Prevalence similar in type 1 and 2 • Cutaneous infections are more common in

type 2, whereas autoimmune-related lesions in type 1• Good metabolic control may prevent and help

cure some

Classification

• Vascular• Metabolic• Necrobiotic• Bullous• Infections• Neuropathic• Treatment-related• Miscellaneous

Dermatologic manifestations of diabetes• Vascular• Metabolic• Necrobiotic• Bullous• Infections• Neuropathic• Treatment-related• Miscellaneous

Diabetic dermopathy

• “Shin spots”: multiple round/ oval macules over the shins (thighs, forearms) hyperpigmentation, atrophy• Twice common in (older) men• Should have ≥ 4 lesions• Marker of microvascular disease, high correlation

with diabetic retinopathy

Diabetic dermopathy

• 2ry to ?trauma, ?pyoderma• Represent post-traumatic atrophy and post-

inflammatory hyperpigmentation in poorly vascularised skin• Endothelial proliferation, PAS+ deposits in the

BM of blood vessels• Require no Rx

Rubeosis facei (diabeticorum)• Rosy redness of the face• Evident in newly diagnosed diabetics• Up to 60% hospitalised patients with diabetes • Associated with vascular tone and ↑viscosity

(functional microangiopathy)• Often a sign of poor glycaemic control• Returns to normal with improved control

Erysipelas-like erythema

• Well-demarcated red areas in feet & legs• Painless, Lack of systemic signs of infection• Seen in elderly diabetics (majority > 73 years,

duration of diabetes 5.4 years)• Underlying bone destruction+/-• Compensatory ↑ peripheral microcirculation

caused by perfusion due to large vv. disease• Spontaneous resolution over weeks but may

recur

Erysipelas-like erythema

Pigmented purpura

• RBC extravasation from superficial plexus• Cayenne pepper spots (red macules) orange

tan patches• Frequently associated with diabetic dermopathy

(50%)• ↑incidence in elderly diabetics with cardiac

failure • Marker of microvascular disease

Periungulal telangiectasia

• Seen in up to 49% diabetics• Megacapillaries and irregularly elongated loops• Often associated with nail fold erythema,

accompanied by fingertip tenderness and “ragged” cuticles• Functional microangiopathy (engorgement of

venular limbs), tortuosity indicates structural changes

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erysipelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Necrobiotic• Bullous• Infections• Neuropathic

• Treatment-related• Miscellaneous

Acanthosis nigricans

• Symmetrical• Velvety verrucous hyperpigmented plaques• Associated with papillomatous skin tags• Axilla, nape of the neck• Occasionally hands & feet, mucous membranes• Hyperinsulinaemia stimulate IGF receptor on

KC + dermal fibroblasts• Rx: Weight Mx, keratolytics, topical retinoic acid

Acanthosis nigricans

Hyperkeratosis

Papillomatosis

Acanthosis

melanin in basal layer

Eruptive xanthomas

• Occur in less than 0.1% of diabetic patients• Crops of small (1- to 4-mm) yellow papules with

an erythematous halo• May be pruritic and tender• Buttocks and extensor surfaces• Appear in association with elevated triglycerides• Resolve with treatment of ↑glucose and lipid

Yellow skin and nails

• Prevalence 40% in T2DM, more common in elderly• Most evident in distal end of hallux• Caused by: • Hypercarotinaemia• Protein glycosylation end products

Diabetic scleredema

• Non-enzymatic glycosylation of collagen• Fingers and dorsum of the hands, with limited

joint mobility, Huntley’s papules (8-50% type 1 diabetics) • Chest, neck, shoulders - ↑Dermal thickness,

difficult to tent the skin; (common in older type 2 diabetics), Peau d’orange app.• May be subclinical• ?improves with tight glycaemic control

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erisypelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic scleredema

• Necrobiotic

• Bullous• Infections• Neuropathic• Treatment-related• Miscellaneous

Nerobiosis lipoidica

• 0.3- 0.7% of diabetics• Case series of 171 patients, 60% diabetes, 20%

IGT• In 15% patients precede the development of

diabetes by ≈2yrs• More common in females, Caucasians, type 1• Mean age of onset ≈ 34 years

Nerobiosis lipoidica

• Well-circumscribed papules radial expansion sharply-demarcated slightly depressed yellow waxy plaques with erythematous raised border central atrophy with telangiectasia

Nerobiosis lipoidica

• Pretibial, medial malleolus• 15% outside legs• Ulcerate in 1/3 patients• Persists despite glycaemic control• Chronic course, 20% remit spontaneously in 6-

12/12• Rx: intralesional steriods, aspirin, pentoxifylline

Disseminated granuloma annulare• No clearly established association between

localized form and diabetes• Papules and annular lesions with raised skin

coloured / erythematous border and flat center• Symmetrically distributed on the arms, neck, and

upper half of the trunk and less often on the legs• Runs a protracted course

Disseminated granuloma annulare• Sporadic therapeutic success reported with

intralesional/ topical/ systemic steroids, isotretinoin, chlorambucil, cryotherapy, chloroquine, nicotinamide, dapsone, and PUVA

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erysipelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic scleredema

• Necrobiotic• Necrobiosis lipoidica• Disseminated GA

• Bullous• Infections• Neuropathic• Treatment-related• Miscellaneous

Bullous diabeticorum

• More common in type 1, males• Usually confined to feet, occasionally hands• Spontaneous, not related to trauma or infection• Blisters contain sterile clear fluid, rest on a non-

erythematous base• Heal in 2-3 weeks without scarring

3 types1. Common type: clear sterile blisters on tips of

toes/ fingers. Heals without scarring. intraepidermal cleavage.

2. Haemorrhagic bullae: heals with scarring, Cleavage - DEJ

3. Multiple tender non-scarring blisters in sunexposed areas. IMF and porphyrins –ve. Cleavage - lamina lucida

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erisypelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic scleredema

• Necrobiotic• Necrobiosis lipoidica• Disseminated GA

• Bullous• Bullous diabeticorum

• Infections• Neuropathic• Treatment-related• Miscellaneous

Bacterial infections

• Staphylococcal : furuncle, carbuncle, ecthyma• Strep pyogenes : cellulitis, erysipelas• Pseudomonas spp.:• Malignant otitis externa: cellulitis, osteomyelitis,

meningitis, CR nerve palsies, mortality 50% Rx: IV quinolone• Toe nail infection• Toe web infection

Bacterial infections

• Erythrasma• Chronic, asymptomatic symmetric red scaly

macerated plaques in the axillae and groin• Corynebacterium minutissimum• Rx- topical/ systemic erythromycin

• Non-clostridial gas gangrene• Develops in soft tissue near a gangrenous focus• E.coli, klebsiella, pseudomonas and bacteriodes

Fungal infections

• Candida • Oral, perliche• Vaginal/ balanoprosthitis• Intertrigenous skin incl. toe web• Paronychia• Nail infection

• Dermatophytosis• Incidence not ↑ in diabetes• Commonly caused by Trichophyton rubrum, T

mentagrophytes, and Epidermophyton floccosum

Rhinocerebral mucormycosis• Esp. associated with ketosis• Black crust/ pus in terbinate, nasal septum,

palate and orbit• Cerebral involvement in 2/3• Rx: debridement + IV amphotericin + Rx

ketosis • High mortality

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erisypelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic scleredema

• Necrobiotic• Necrobiosis lipoidica• Disseminated GA

• Bullous• Bullous diabeticorum

• Infections• Bacterial• fungal

• Neuropathic• Treatment-related• Miscellaneous

Neuropathic • Anhidrosis • Hyperhidrosis • Neuropathic ulcers : circular, punched out ulcer

in the middle of a callosity over metatarsal heads

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erisypelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic sclredema

• Necrobiotic• Necrobiosis lipoidica• Disseminated GA

• Bullous• Bullous diabeticorum

• Infections• Bacterial• fungal

• Neuropathic• Anhidrosis/hyperhidrosis• Neuopathic ulcers

• Treatment-related• Miscellaneous

Insulin reactions

• Immediate• Localized/ Generalised erythema, urticaria

• Delayed• Itchy nodule 4-24 h after injection

• Lipoatrophy• Circumscribed depressed areas 6-24/12 after starting Rx• lypolytic component of inulin preparation, immune complex

mediated inflammation• Less common with purified recombinant human insulins

• Lipohypertrophy • Soft nodules resembling lipoma• Local response to lipogenic action of insulin• Preventable by rotating injection sites

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erisypelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic sclredema

• Necrobiotic• Necrobiosis lipoidica• Disseminated GA

• Bullous• Bullous diabeticorum

• Infections• Bacterial• fungal

• Neuropathic• Anhidrosis/hyperhidrosis• Neuopathic ulcers

• Treatment-related• Insulin reactions• Photosensitivity, lichenoid Rn

• Miscellaneous

Acquired Perforating Dermatoses

• Umbilicated hyperpigmented papules with a central keratotic plug• Common site = extensor surfaces of extremities• Pruritus a major symptom• Strong association with ESRD• Histology shows transepidermal elemination of

degenerative elastic/ collagen fibres• Treatments: Topical tretinoin, phototherapy

Vitiligo

• Localised/ generalised forms• 1-7% in type 1 diabetics (0.2-1% in general

population)• May be a part of polyglandular syndrome type 1• Rx: sun protection, topical/ systemic steriods,

phototherapy

Lichen planus

• Polygonal erythematous flat lesions• Wrist, dorsa of feet, lower legs• Oral/ genital lesions: white lacy pattern• DD- lichenoid drug reactions • Rx: topical steriods

Dermatologic manifestations of diabetes• Vascular• Diabetic dermopathy• Rubeosis facei• Erisypelas like erythema• Pigmented purpura• Periungual telangiectasia

• Metabolic• Acanthosis nigricans• Eruptive xanthoma• Yellow skin and nails• Diabetic scleredema

• Necrobiotic• Necrobiosis lipoidica• Disseminated GA

• Bullous• Bullous diabeticorum

• Infections• Bacterial• fungal

• Neuropathic• Anhidrosis/hyperhidrosis• Neuropathic ulcers

• Treatment-related• Insulin reactions• Photosensitivity

• Miscellaneous• APD ◦ vitiligo• pruritus ◦ lichen planus

Key points

• Diabetic dermopathy (shin spots) is considered to be the most common dermatologic manifestation of diabetes.• Skin manifestations of diabetes may also serve as

ports of entry for secondary infection.• A candidal infection can be an early sign of

undiagnosed diabetes.• NLD is not pathognomonic to diabetes, as about a

third do not have diabetes.• Diabetic scleredema may present as limited joint

mobility of hands.

References

1. Hattem SV, Bootsma AH, Thio HB. Skin manifestations of diabetes. Cleaveland clinic J of Med. 2008; 75 (11): 772-87

2. Morgan AJ . Diabetic dermopathy: A subtle sign with grave implications. J Am Acad Dermatol - 2008; 58(3): 447-51

3. Perez M, Kohn S. Cutaneous Manifestations of Diabetes Mellitus. Journal of the American Academy of Dermatology. 1994; 30 (4): 519-531