Diabetes Research and Clinical Practice 39 (1998) 101 106

Skin lesions in diabetes mellitus: prevalence and clinical correlations

G. Romano a, G. Moretti b, A. Di Benedetto a, C. Giofre ` b, E. Di Cesare a, G. Russo a, L. Califano b, D. Cucinotta a,*
a b

Department of Internal Medicine, Policlinico Uni6ersitario, 98100 Messina, Italy Institute of Dermatology, Uni6ersity of Messina Medical School, Messina, Italy

Received 12 May 1997; received in revised form 27 October 1997; accepted 20 November 1997

Abstract With the aim to assess the prevalence and the main clinical correlations of skin lesions in diabetes mellitus, 457 diabetic subjects consecutively attending an outpatient clinic underwent a dermatological examination. Neurovascular foot lesions were excluded. Thirty-ve of 64 IDDM patients (54%) had skin alterations mainly consisting of vitiligo (9% of all patients), psoriasis (9%) and eczema (8%). The most frequent skin lesions observed in 240/393 NIDDM subjects (61%) were represented by infections (20% of all patients) and diabetic dermopathy (12.5%), while other lesions were not common. NIDDM patients with skin infections had a worse metabolic control, and those with diabetic dermopathy had a greater prevalence of neuropathy and large vessel disease than patients without skin lesions. These data show that the prevalence of skin diseases in a large, unselected diabetic population is higher than expected and indicate that, in most cases, a careful dermatological examination and a better metabolic control are needed in order to improve quality of life in these patients. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Skin lesions; Diabetes mellitus; IDDM; NIDDM; Metabolic control

1. Introduction Skin lesions are frequently observed in diabetic patients and it is generally stated that about 30%

* Corresponding author. Tel.: + 39 90 2212390; fax: + 39 90 2935162; e-mail: cucinotd@imeuniv.unime.it

of these patients have cutaneous disorders [13]. According to a recent review [4], cutaneous manifestations of diabetes mellitus can be classied in four categories: skin diseases with strong to weak association with diabetes (necrobiosis lipoidica, diabetic dermopathy, diabetic bullae, yellow skin, eruptive xanthomas, perforating disorders, acanthosis nigricans, oral leucoplakia, lichen planus), infections (bacterial, fungal), cutaneous

0168-8227/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S 0 1 6 8 - 8 2 2 7 ( 9 7 ) 0 0 1 1 9 - 8

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manifestations of diabetic complications (microangiopathy, macroangiopathy, neuropathy) and skin reactions to diabetic treatment (sulphonylureas or insulin). The frequency of skin lesions in diabetes is not well known; some cutaneous disorders are clearly more frequent in diabetes, but it is difcult to understand the exact nature of this association; moreover data concerning the epidemiology of these lesions come from former studies [1,5,6] and no recent reports are available. Aim of this study was to evaluate the prevalence and the main clinical characteristics of skin disorders in a large, unselected population attending an outpatient diabetes clinic. 2. Subjects and methods Four hundred and fty-seven patients, consecutively attending the outpatient diabetes clinic at the University of Messina Medical School Hospital, underwent a complete dermatological examination. Only patients with types of diabetes other than insulin-dependent (IDDM) or non-insulindependent (NIDDM) were excluded from the study. According to WHO criteria [7], 64 patients had IDDM (38 males, mean age 22 9 8 years, mean diabetes duration 10 9 4 years) and 393 had NIDDM (170 males, mean age 59 9 16 years, known diabetes duration 14 9 7 years). Chronic complications of diabetes were assessed according to standard clinical and instrumental evaluations: retinopathy was diagnosed by means of evidence of background or proliferative lesions at ophthalmoscopy; nephropathy by means of albuminuria (urinary albumin excretion rate \ 30 mg/24 h); and peripheral neuropathy by means of a positive diabetic neuropathy index [8]. Finally, large vessel disease was diagnosed on the basis of clinical records and/or ECG evidence of coronary heart disease, according to the Minnesota codes [9]. Metabolic control at the visit was assessed by means of glycosylated haemoglobin HbA1c (HPLC, Diamat-Biorad, Milan, Italy). According to HbA1c values, patients were classied as well controlled (HbA1c B 7.2%, n = 110), fairly controlled (HbA1c \ 7.2 and 5 9%, n = 196) and poorly controlled (HbA1c \ 9%, n = 151).

Dermatological examinations were always performed by the same two trained physicians during a morning routine visit at the outpatient clinic. When more than one skin lesion occurred (as in 24 patients) the clinically most relevant one was considered. Cutaneous manifestations of diabetic complications (neurovascular foot lesions) were excluded from the evaluation. Results are expressed as mean 9 standard deviation. Statistical analysis was performed using the Students t -test for unpaired data and X 2-test. P values were based on a two-sided test of statistical signicance.

3. Results In the whole diabetic population 276/457 (60%) patients had skin disorders; the prevalence did not differ between IDDM (35/64 patients, i.e. 55%) and NIDDM (240/393 patients, i.e. 61%) but the kinds of lesions were clearly different. Skin lesions observed in IDDM patients are reported in Table 1; the most frequent were vitiligo and psoriasis, followed by xerosis, warts, eczema and candida infections, without differences among patients with good, fair or poor metabolic control. In NIDDM patients the most frequent skin lesions were infections and diabetic dermopathy, observed in 20.6 and in 12.5% of all patients, respectively. Also psoriasis, pruritus, xerosis, lichen and cutaneous complications of diabetes treatment were observed, while other skin lesions were rare. Moreover, the frequency of skin infections was signicantly higher in poorly controlled patients than in those with a good metabolic control (Table 2). Among skin infections, the most common were dermatophytosis and candida infections, while bacterial or viral infections were less often observed (Table 3). Skin infections were mainly localized at the interdigital spaces, skin folds and genitalia, while diabetic dermopathy was almost exclusively observed in the pretibial region (Table 4). Cutaneous complications of diabetes therapy consisted of local allergic reactions of the delayed type, observed in 6/164 patients treated with hu-

G. Romano et al. / Diabetes Research and Clinical Practice 39 (1998) 101106 Table 1 Skin lesions observed in 64 consecutive IDDM patients Lesion Affected patients (% of all IDDM patients) 6 6 5 4 4 3 2 2 2 1 35 (9) (9) (8) (6) (6) (5) (3) (3) (3) (2) (54%) Well-controlled patients 2 1 1 0 1 1 1 0 1 0 8 Fairly controlled patients 3 2 2 2 2 2 0 1 0 1 15 Poorly controlled patients 1 3 2 2 1 0 1 1 1 0 12

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Vitiligo Psoriasis Eczema Warts Xerosis Candida infections Tinea infections Pityriasis Skin tags Prurigo Total

man insulins, and of urticarial eruptions in 3/197 of all patients taking oral hypoglycaemic drugs (sulphonylureas and/or biguanides). NIDDM patients with the most frequent skin lesions were then divided into ve subgroups, according to the kind of dermopathy and were compared with patients without lesions. No differences were observed concerning age, diabetes duration, prevalence of microangiopathy (both retinopathy and nephropathy) and of insulin treatment; on the contrary, patients with skin infections had a worse metabolic control and patients with diabetic dermopathy had a greater prevalence of neuropathy and large vessel disease than patients without skin lesions (Table 5).

4. Discussion These data demonstrate that the prevalence of skin lesions in a large, unselected diabetic population is greater than generally reported, since 60% of our patients show cutaneous diseases. This high prevalence equally affects IDDM and NIDDM patients but the nature of skin lesions is very different in the two types of diabetes. In NIDDM patients the most frequent skin disease is represented by skin infections, especially dermatophytosis and candidosis, which were observed in more than 20% of all patients, while the prevalence of other lesions is clearly lower. In IDDM patients,

vitiligo, psoriasis and eczema are the most common skin diseases, and their high frequency can be explained by the common immunological background with this type of diabetes; the relatively small number of patients, however, does not allow denite conclusions. On the contrary, in the large NIDDM group the high prevalence of skin infections is signicantly associated with a worse metabolic control, as indicated by the greater prevalence of infections in patients with poor control and the higher mean HbA1c levels observed in patients with skin infections. It is widely believed that diabetic patients have an increased risk for infectious diseases, although there is little documented evidence to support it. This risk seems to be higher in poorly controlled patients, but it is often difcult to understand whether poor metabolic control is the cause or the consequence of the concurrent infectious illness. It has been suspected that a poor metabolic control affects host defences, since some abnormalities in white cells functions (impaired killing) have been observed under conditions of hyperglycaemia and ketosis [10] or hyperglycaemia alone [11], and this could explain the increased prevalence of infections in poorly controlled diabetic patients [12], also in our series. On the other hand, it is possible that skin infections, as with other infections [13], cause a deterioration in the degree of metabolic control and are the cause of the increased HbA1c levels we have

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Table 2 Skin lesions observed in 393 consecutive NIDDM patients Lesion Affected patients (% of all NIDDM patients) (20.6) (125) (4.6) (4.3) (3.8) (2.5) (2.5) (1.5) (1.5) (1.3) (1) (0.8) (0.8) (0.8) (0.8) (0.5) (0.5) (0.3) (0.3) (0.3) (61.2) Well-controlled patients 14 18 7 6 5 4 5 4 1 2 3 1 1 2 1 2 0 0 1 1 78 Fairly controlled patients 32 13 6 4 7 5 3 1 3 3 0 0 2 1 1 0 0 1 0 0 82 Poorly controlled patients 35* 18 5 7 3 1 2 1 2 0 1 2 0 0 1 0 2 0 0 0 80

Infections 81 Diabetic dermopathy 49 Psoriasis 18 Prurigo 17 Lichen planus 15 Warts 10 Xerosis 10 Reaction to insulin 6 Rosacea 6 Skin tags 5 Necrobiosis lipoidica 4 Reaction to oral agents 3 Vitiligo 3 Eruptive xanthomas 3 Rubeosis diabeticorum 3 Diabetic bullae 2 Purpuric dermatoses 2 Yellow skin 1 Scleroderma diabeticorum 1 Granuloma annulare 1 Total 240

*2PB0.01 vs. well-controlled patients.

observed; moreover skin infections have been also recorded, to a lesser extent, in well-controlled patients. Therefore we cannot exclude that unknown factors other than metabolic control inuence the increased risk for skin infections in our patients. It is interesting to note that in our experience cutaneous infections are almost exclusively sustained by fungal agents (81% of all cases), while bacterial or viral agents are clearly less frequent.
Table 3 Kind of infection observed in 81 NIDDM patients with skin infections Infection Dermatophytosis Candida infection Bacterial infection Herpes infection Total No. of patients 37 28 10 6 81 % of all patients 46 35 12 7 100

We have no data to explain this difference, but it is possible that a less evident clinical symptomatology or a greater resistance to the common antiseptic measures, with respect to the other infective agents, justify this higher prevalence of
Table 4 Localization of the two most frequent skin lesions in NIDDM patients Infections (n = 81) Localization Oral mucosa Genitalia Skin folds Interdigital spaces Nails Truncus Upper limbs Lower limbs n 6 15 16 21 7 6 3 7 Diabetic dermopathy (n = 49) Localization Lower limbs Upper limbs Truncus n 43 4 2

Table 5 Clinical and metabolic parameters in NIDDM patients, according to the most frequent skin lesions No lesions (n = 153) 61.5+11.3 45.7 12.2 9 8.9 8.1 9 1.5 21.6 44.4 18.3 27.5 40.5 59.8 9 13.6 40.1 11.2 9 8.3 8.8 9 1.7* 25.9 49.1 22.2 29.6 43.2 62.3 9 8.7 46.9 12 9 8.4 8.2 9 1.3 53.1* 46.9 24.5 42.9* 42.8 63.1 9 8.6 44.4 11.1 9 8.1 7.8 9 7.9 22.2 38.9 22.2 33.3 44.4 Infections (n = 81) Diabetic dermopathy (n = 49) Psoriasis (n = 18) Prurigo (n = 17) 59.7 9 14 47 9.5 9 5.6 8.3 9 1.1 23.5 47 17.6 29.4 41.2 Lichen (n = 15) 56 9 6.5 40 8.8+6.5 7.9 9 0.7 20 40 20 26.6 46.6

Parameter

Age, years (mean 9 S.D.) Sex, males (%) Diabetes duration, years (mean 9 S.D.) HbA1c, % (mean 9 S.D.) Prevalence of large vessel disease (%) Prevalence of retinopathy (%) Prevalence of nephropathy (%) Prevalence of neuropathy (%) Prevalence of insulin treatment (%)

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*2PB0.01 vs. patients with no lesions.

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fungal infections. Another discrepancy concerns the prevalence of skin infections in patients with NIDDM and in those with IDDM, where this prevalence is lower. This discrepancy could be explained by the younger age and shorter diabetes duration and by a better level of disease knowledge and self-care in IDDM patients; however, as previously stated, the small number of IDDM subjects in our series makes difcult any comparison. The prevalence of other skin lesions in our experience is somewhat different from that previously reported: diabetic dermopathy affects 12.5% of our NIDDM patients, a percentage that is clearly lower than in other reports [14,15]; moreover, it is more frequent in patients with neuropathy or large vessel disease, but not in those with clinical evidence of microangiopathy, both at renal and retinal levels. These ndings are partly in contrast with some previous reports, showing an unexplained association between diabetic dermopathy and retinopathy [16], but agree with the formerly observed association with neuropathy [17]. Taken together, these observations further support the widespread opinion that this dermopathy reects the severity of diabetes and its complications [2]. Other cutaneous diseases, which have been considered as associated with diabetes, are generally rare in our patients, as demonstrated by the very low prevalence of necrobiosis lipoidica, diabetic bullae, yellow skin, scleredema, granuloma annulare; on the contrary we observed a relatively high prevalence of psoriasis and prurigo (4.6 and 4.3% of all NIDDM patients, respectively). Finally, cutaneous reactions to insulin were only observed in 3.4% of all insulin-treated patients; the exclusive use of human insulin in our patients can explain this low prevalence. In conclusion, this report shows that in our outpatient diabetic population there is a high prevalence of skin lesions, mainly represented by cutaneous infections in poorly controlled NIDDM patients and immune-related disorders in IDDM subjects. A frequent dermatological survey and a better metabolic control are probably needed to improve prognosis and quality of life of these patients. .

References
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