|Year : 2013 | Volume
| Issue : 2 | Page : 56-62
Skin manifestations in Egyptian diabetic patients: a case series study
Eman M Sanad1, Mona M ElFangary2, Neveen E Sorour1, Noha M ElNemisy1
1 Department of Dermatology and Andrology, Banha, University, Banha, 6th of October City, Egypt
2 Department of Dermatology and Andrology, Misr University for Science and Technology (MUST), 6th of October City, Egypt
|Date of Submission||11-Oct-2013|
|Date of Acceptance||11-Nov-2013|
|Date of Web Publication||31-Dec-2013|
Mona M ElFangary
Department of Dermatology, Misr University for Science and Technology (MUST), Almotamayez District, 6th of October City, P.O.Box: 77
Source of Support: None, Conflict of Interest: None
Skin manifestations in diabetes mellitus (DM) are quite common. Skin changes can manifest in the prediabetic stage, in the acute metabolic situation and in the late diabetic degenerative stage.
To study the prevalence and the pattern of cutaneous manifestations among diabetic patients to aid in better management of diabetic skin diseases.
Patients and methods
One hundred patients with DM having at least one skin manifestation were selected and subjected to a detailed dermatological and systemic examination, and the findings were recorded. Blood samples were obtained for random blood glucose level.
The most prevalent findings were cutaneous infections (40%), followed by pruritus (11%), local reactions at the site of insulin injection (8%), vitiligo (8%), diabetic dermopathy (7%), periungual telangectasia (6%), and xanthelasma (5%). The prevalence of skin manifestations was higher as the duration of diabetes increased and was more in type II than in type I diabetic patients.
The early detection of skin manifestations in DM is of prime importance to be able to avoid and/or properly manage the complications and prevent disability.
Keywords: cutaneous manifestations, Diabetes mellitus, Egyptian patients, skin manifestations.
|How to cite this article:|
Sanad EM, ElFangary MM, Sorour NE, ElNemisy NM. Skin manifestations in Egyptian diabetic patients: a case series study. Egypt J Dermatol Venerol 2013;33:56-62
|How to cite this URL:|
Sanad EM, ElFangary MM, Sorour NE, ElNemisy NM. Skin manifestations in Egyptian diabetic patients: a case series study. Egypt J Dermatol Venerol [serial online] 2013 [cited 2018 Sep 18];33:56-62. Available from: http://www.ejdv.eg.net/text.asp?2013/33/2/56/123941
| Introduction|| |
The skin has the potential to provide a window into the patient and aid in the diagnosis of diseases of all organ systems  . Diabetes mellitus (DM) affects every organ system and the skin is no exception. Approximately one-third of diabetic patients have cutaneous manifestations. In fact, cutaneous findings may be the first indicator of disease and may allow an astute physician to initiate diagnostic testing  .
The pathogenesis of these cutaneous manifestations as well as the internal complications is multifactorial and arises from a complex interplay between biochemical, vascular, immune and metabolic alterations that occur in a diabetic state  .
The biochemical process of advanced glycation in particular seems to be accelerated in diabetes as a consequence of chronic hyperglycemia. Advanced glycation involves the nonenzymatic modification of proteins, lipids and nucleic acids by reducing sugars, generating a heterogeneous group of chemical moieties recognized as advanced glycated end products (AGE)  . The interaction between an AGE and its receptor (RAGE), expressed in a variety of cells, leads to increased proinflammatory cytokines and generates oxidative stress and subsequently evokes vascular inflammation and thrombosis  . Thus, AGEs are hypothesized to play a vital role in the pathogenesis of diabetic complications.
Skin is rich in collagen, which is very prone to form and deposit AGEs during long-term hyperglycemia  . As keratinocyte is the most important cell to maintain and regulate the epidermal barrier function, Park et al.  presumed that AGE-RAGE interactions in epidermal keratinocytes may also cause impaired barrier homeostasis including permeability and antimicrobial barriers, which could be a major pathophysiology of underlying cutaneous complications observed in DM.
Almost all diabetic patients eventually develop skin complications from the long-term effects of DM on the microcirculation and on skin collagen. Also, insulin and oral hypoglycemic drugs can have dermal side effects. Furthermore, diabetes-related cutaneous lesions may serve as a port of entry for secondary infections  .
This epidemiological study throws light on the prevalence, the pattern and the importance of cutaneous manifestations in diabetes, to be able to recognize these signs and symptoms and aid in their prevention and treatment.
| Patients and methods|| |
One hundred patients with DM of different durations were selected from Banha University Hospital, Qualyobia Governorate, and El-Menshawy hospital, Tanta District, Gharbeya Governorate, during the period from March 2011 to March 2012. The study was approved from Research Ethics Committee of the faculty of medicine in Benha University. The patients were of different sex and age, of either type I or type II DM and having at least one skin manifestation.
Each patient was subjected to a complete history taking, thorough dermatologic and systemic clinical examinations, blood analysis for random blood glucose (RBG) level and signed an informed consent. Photography of the skin manifestations was carried out, and relevant microbiological and histopathological investigations to confirm the diagnosis were carried out.
The collected data were analyzed using the statistical package for the social sciences (SPSS Inc., Chicago, Illinois, USA) version 16. Quantitative data were analyzed using mean and SD, whereas frequency and percentage were used with qualitative data. The paired t-test was used to compare means of different groups, whereas the Z-test and the χ2 -test were used to compare frequencies. A P value less than 0.05 was considered statistically significant.
| Results|| |
This study was conducted on 100 diabetic patients, all having one or more cutaneous manifestations (three patients had three skin manifestations, 19 had two and 79 had one skin manifestation). Seventy-seven patients were of type II DM (noninsulin dependent) and 23 patients were of type I DM (insulin dependent). The patients included 15 men (10 type II and five type I) and 85 women (67 type II and 18 type I), with their age ranging from 17 to 80 years, with a mean of 51.42 ± 14.66 years. The duration of the disease ranged from 3 months to 30 years with a mean of 10.57 ± 7.63 years. The duration of DM was more than 5 years in 65 patients and 5 years or less in 35 patients. Referring to the files, 70 patients had a history of diabetic ketoacidosis (DKA), 13 patients had one attack and 57 patients had DKA more than once.
In this study, the most common skin disorders were cutaneous infections (40%), followed by pruritis (11%), local reactions at the site of insulin injection (8%), vitiligo (8%), diabetic dermopathy (7%), periungual telangectasia (6%), and xanthelasma (5%). Diabetic bullae, reactions of oral hypoglycemic drugs, skin tags, and neuropathic ulcers occurred in 4% of the patients, whereas acanthosis nigricans, angular cheilitis, and xerosis in 3% and diabetic rubeosis, stiff joints, necrobiosis lipoidica diabeticorum, psoriasis, and eczema were observed in 2% of the patients. Yellow nail, pigmented purpura, keratosis pilaris, acquired ichthyosis, and pemphigus vulgaris were each observed in 1% of the patients.
Cutaneous infections included fungal (22%), bacterial (16%), and viral (2%) infections. Tinea pedis was the most common fungal infection (12%), whereas boils were the most common bacterial infection (5%). Among viral infections, one patient had herpes simplex and another had herpes zoster.
Systemic diseases were present in 47 patients (47%); hypertension was the most common, either alone (24 patients) or with other systemic diseases (seven patients) such as cardiac, renal and hepatic diseases, which also occurred without hypertension.
Although the number of male patients in our study was small (15), necrobiosis lipoidica and psoriasis were present only in men and diabetic dermopathy was present more often in men than in women (5 : 2).
Type II DM showed a larger number of patients suffering from skin manifestations, but there was no statistically significant relation between the pattern of skin manifestations of DM and the type of DM, except for xanthelasma and boils, which were significantly present in type II DM (P = 0.047; [Table 1], [Table 2] and [Table 3]).
|Table 1: Relationship between skin manifestations of DM and the type of DM |
Click here to view
|Table 2: Relationship between skin fungal infections and the type of DM |
Click here to view
|Table 3: Relationship between skin bacterial infections and the type of DM |
Click here to view
The number of patients suffering from skin manifestations increased with a longer duration of DM, but there was no statistically significant relation between skin manifestations of DM and the duration of DM, except for diabetic bullae (P = 0.04), diabetic dermopathy (P = 0.003), and tinea pedis (P = 0.001), which were significantly present in DM of more than 5 years' duration [Table 4], [Table 5] and [Table 6].
|Table 4: Relationship between skin manifestations of DM and the duration of DM |
Click here to view
|Table 5: Relationship between skin fungal infections and the duration of DM |
Click here to view
|Table 6: Relationship between skin bacterial infections and the duration of DM |
Click here to view
Patients with a history of DKA more than once had a larger number of cutaneous manifestations (57%), with only diabetic bullae showing statistical significance (P = 0.03).
Local insulin reactions (8%) were in the form of ecchymosis, hyperpigmentation or erythematous papules at the site of injection, whereas drug reactions of oral hypoglycemic drugs (4%) were in the form of photosensitivity, maculopapular eruptions and urticaria. A statistically significant relation was found between local insulin reactions and RBG greater than 200 (P = 0.001) (7of 8 patients had RBG > 200), whereas all patients (four) with reactions to oral hypoglycemic drugs had RBG greater than 200.
| Discussion|| |
Cutaneous signs of DM are extremely valuable to the clinician. They generally appear after the primary disease has developed, but may signal or appear coincidentally with its onset, or even precede diabetes by many years  .
Cutaneous manifestations of diabetes are classified into four categories: Skin lesions with a 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 manifestations of diabetic complications (microangiopathy, macroangiopathy, neuropathy), and skin reactions to diabetic treatment (sulfonylureas or insulin)  .
Skin infections were the most common skin manifestations observed in this study, reported in 40 patients (40%). These results are in agreement with other authors reporting a range between 30 and 40% , . The greater frequency of infections in diabetic patients is caused by the hyperglycemic environment that favors immune dysfunction (e.g. damage to the neutrophil function, depression of the antioxidant system, and humoral immunity), microangiopathies and macroangiopathies and neuropathy  . Also, the impairment of skin barrier function, the hypohidrosis and the decreased epidermal antimicrobial peptide expression in the skin due to long-standing hyperglycemia could be other causes of skin infections in DM  , predisposing the already susceptible diabetic patients to chronic and recurrent infections.
In this study, fungal infections were the most prevalent, affecting 22% of our patients, followed by bacterial infections at 16%. Shahzad et al.  reported 28.1% fungal and 5% bacterial infections. Tinea pedis was the most common fungal infection affecting 12% of our patients, whereas Shahzad et al.  reported 21.9%. This difference may be due to the variation in climate and humidity. Boils were the most common bacterial infection in this study (5%) similar to Goyal et al.  (6%), whereas Shahzad et al.  reported cellulitis (1.9%).
Generalized pruritus was reported in 11% of our patients, a percentage higher than other studies that reported 7.1  and 9.9%  , but less than Goyal et al.  who reported 30%. The cause and effect of pruritus in DM remain unproven. Metabolic abnormalities, autonomic dysfunction, anhydrosis, and diabetic neuropathy may all contribute  . Also, it is well known that pruritus occurs frequently with dry skin. In DM, dry skin occurs due to impaired skin barrier function and hypohydrosis, which may lower the threshold for itching  .
In this study, local reactions at the site of insulin injection were reported in 8% of the patients, whereas Shahzad et al.  reported 2.7%. Local skin reactions to insulin therapy became a rare complication since the general use of highly purified human insulin and newer delivery systems. The change to short-acting insulin analogue as a less allergenic substance, insulin desensitization or the usage of insulin pumps as continuous subcutaneous insulin infusion may represent a successful alternative treatment in diabetic patients presenting local or generalized allergy to insulin  . Reactions to oral hypoglycemic drugs in this study were reported in 4% of the patients, whereas it was 1.3% in Shahzad et al.  and none of the patients was reported in another study  . The increase of local insulin and oral hypoglycemic drug reactions in the present study may be because these patients (11 of 12 patients) were not well controlled with their RBG greater than 200, and a statistically significant relation was present.
Vitiligo was reported in 8% of our patients, which was similar to Goyal et al.  , whereas Ahmed et al.  reported 5.7%. Vitiligo is a consistent finding in the literature concerning skin complications of diabetes. Vitiligo and diabetes may have a causal relationship and both are associated with autoimmunity. Familial-hereditary tendencies occur in both diseases. There are neuropathic complications in diabetes, and in vitiligo, a dermatodermal variety occurs with evidence of degenerated nerve endings. In diabetes, the products of oxidative stress, free radical generation, and release of various growth factors may be cytotoxic, affecting melanogenesis  .
Diabetic dermopathy was reported in 7% of our patients, whereas other studies reported 11.2%  and 4.2%  . It has been reported that diabetic dermopathy is the most common cutaneous marker of diabetes in the literature, varying from 12.5 to 40%  . It is a cutaneous manifestation of diabetic microangiopathy. An association between diabetic dermopathy and large-vessel disease (particularly coronary artery disease), neuropathy, nephropathy, and retinopathy has been identified. Thus, diabetic dermopathy may be a clinical marker for the severity of systemic diabetic complications  .
In this study, periungual telangiectasia was reported in 6% of the patients. Prevalence up to 49% has been described in all diabetic patients  . Venous capillary dilatation of the periungual microcirculation appears to be an excellent indicator of functional microangiopathy. In diabetes, periungual telangiectasia is often associated with nail fold erythema, accompanied by fingertip tenderness and ragged cuticles  .
Xanthelasma was reported in 5% of the patients in this study, whereas Goyal et al.  reported 10% in his study of one hundred patients with DM. Diabetic patients often suffer from high lipid (cholesterol and triglycerides) levels in the blood. This causes fat to be deposited in the skin and presents as xanthomas or xanthelasma.
Spontaneous presentation of bullae, particularly isolated at the acral limbs, should alert physicians to screen for diabetes  . Although rare, diabetic bullae were reported in 4% of our patients, whereas other studies reported 0.6%  , 2%  , and 2.2%  .
In this study, skin tags (acrochordons) were reported in 4% of the patients, whereas other studies reported 3.7%  , 32%  , and 40.9%  . High insulin levels stimulate keratinocyte proliferation, resulting in the growth of these lesions, and acrochordons may be a cutaneous marker for impaired carbohydrate metabolism  .
In this study, neuropathic ulcers were reported in a lower percentage of patients (4%) compared with 7.2 and 12.9% of the patients in the studies by Shahzad et al.  and Ahmed et al.  , respectively. These ulcers developed in areas of constant pressure. Patients usually suffer from peripheral neuropathy, with loss of protective sensation. Other contributing factors include peripheral vascular disease, trauma, and poor wound healing due to hyperglycemia  .
Acanthosis nigricans was reported in 3% of our patients similar to Ahmed et al.  who reported 2.9% but less than Goyal et al.  who reported 8% of their patients. Acanthosis nigricans is believed to evolve from a complex mechanism ultimately resulting in the interaction between excess insulin and insulin-like growth factor-1 receptor present on keratinocytes and fibroblasts. This interaction stimulates epidermal cell proliferation, leading to the clinical manifestation of hyperkeratosis and acanthosis  .
Xerosis has been reported in only 3% of the patients in the present study, whereas Goyal et al.  and Shahzad et al.  reported 44 and 36.9%, respectively. This difference may be due to regional changes in climate and humidity. The chronic hyperglycemic condition causes marked decrease in stratum cornium hydration proportional to the disease duration, leading to xerosis  . Severe xerotic patients may acquire an ichthyosiform aspect  , and this occurred in only one of our patients. Xerosis may play a significant role in keratosis pilaris development  , which also occurred in one patient.
Rubeosis faciei, due to microangiopathic changes and dilatation of superficial veins of the face  , was present in 2% of the patients in this study. The prevalence in other studies ranged from 3.1%  , 4%  , 7.1%  , and up to 59%  . The venular dilatation may be caused by hyperglycemia-induced sluggish mirocirculation. Moreover, hypertention may exacerbate the capillary damage  .
Stiff joints and clinically apparent thickening of the skin involving the fingers and hands were present in 2% of our patients. The prevalence in other studies ranged from 9 to 58%  . The limited joint mobility syndrome has been correlated with increased frequency of microvascular complications in diabetics to those without limited joint mobility syndrome  .
Necrobiosis lipoidica diabeticorum was reported in 2% of the patients in this study. This is in agreement with other studies that reported 1.4%  and 0.6%  . NLD is relatively uncommon but its presence warrants a thorough workup for diabetes  . Microangiopathic changes, abnormal collagen, altered lipid metabolism and impaired immunity have all been implicated in its pathophysiology  .
Psoriasis and diabetes coexisted in 2% of our patients. There are reports of a significant association of DM and psoriasis in a large series of patients with psoriasis. According to Avci et al.'s study  , individuation of the various hues of erythema in psoriatics by careful dermatological examination or routine measurements of lesional erythema (deep red to purple hue instead of the typical pink to red tones) may alert the physician to possible impaired glucose tolerance in the presenting individual, and this may affect disease severity.
None of the patients in this study had granuloma annulare, scleredema adultorum, reactive perforating collagenosis or lichen planus, although these are usually associated with DM.
Although this study included much fewer male patients than female patients, diabetic dermopathy, psoriasis, and NLD were reported more in men and this is in agreement with other studies , .
This study showed that the prevalence of skin manifestations was higher in type II than in type I diabetic patients, especially cutaneous infections, and as the duration of diabetes increased, the likelihood of developing skin manifestations also increased, and this is similar to other studies , .
Our study also showed that cutaneous manifestations were present more often in patients with a history of DKA more than once (57%). Also, a large number of our patients (47%) were associated with systemic diseases and this is different from another study that reported only 3.2%  ; the difference can be explained by environmental and socioeconomic factors as well as by the degree/extent of accessibility to appropriate medical care.
In conclusion, this study throws light on the importance of the early detection and the understanding of the pathogenesis of skin manifestations in DM, to be able to avoid and/or properly manage the complications and prevent disability.
| Acknowledgements|| |
Conflicts of interest
| References|| |
|1.||Lee A. Skin manifestations of systemic disease. Aust Fam Physician 2009; 38 :498-505. |
|2.||Levy L, Zeichner JA. Dermatologic manifestation of diabetes. J Diabetes 2012; 4 :68-76. |
|3.||Sehgal VN, Bhattacharya SN, Verma P. Juvenile, insulin-dependent diabetes mellitus, type 1-related dermatoses. J Eur Acad Dermatol Venereol 2010; 25 :625-636. |
|4.||Goh SY, Cooper ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93 :1143-1152. |
|5.||Ye X, Tong Z, Dang Y, Tu Q, Weng Y, Liu J, et al. Effects of blood glucose fluctuation on skin biophysical properties, structure and antioxidant status in an animal model. Clin Exp Dermatol 2010; 35 :78-82. |
|6.||Park HY, Kim JH, Jung M, Chung CH, Hasham R, Park CS, et al. A long-standing hyperglycaemic condition impairs skin barrier by accelerating skin ageing process. Exp Dermatol 2011; 20 :969-974. |
|7.||Van Hattem S, Bootsma AH, Thio HB. Skin manifestations of diabetes. Cleve Clin J Med 2008; 75 :772-787. |
|8.||Goyal A, Raina S, Kaushal SS, Mahajan V, Sharma NL. Pattern of cutaneous manifestations in diabetes mellitus. Indian J Dermatol 2010; 55 :39-41. |
|9.||Romano G, Moretti G, Di Benrdetto A, Giofre C, Di Cesare E, Russo G, et al. Skin lesions in diabetes mellitus: prevalence and clinical correlations. Diabetes Res Clin Pract 1998; 39 :101-106. |
|10.||Ahmed K, Muhammad Z, Qayum I. Prevalence of cutaneous manifestation of diabetes mellitus. J Ayub Med Coll Abbottabad 2009; 21 :76-79. |
|11.||Shahzad M, Al Robaee A, Al Shobaili HA, Alzolibani AA, Al Marshood AA, Al Moteri B, et al. Skin manifestations in diabetic patients attending a diabetic clinic in the Qassim region, Saudi Arabia. Med Princ Pract 2011; 20 :137-141. |
|12.||Casqueiro Ju, Casqueiro Ja, Alves C. Infections in patients with diabetes mellitus: a review of pathogenesis. Indian J Endocrinol Metab 2012; 16 :527-536. |
|13.||Braff MH, Bardan A, Nizet V, Gallo RLJ. Cutaneous defence mechanisms by antimicrobial peptides. J Invest Dermatol 2005; 125 :9-13. |
|14.||Sasmaz S, Buyukbese MA, Cetinkaya A, Celi KM, Arican O. The prevalence of skin disorders in type-2 diabetic patients. Internet J Dermatol 2005; 3 :1-7. |
|15.||Butler DF, Elston DM, Flowers F, Wells MJ, Miller JJ, Gelfand JM. Pruritus and systemic disease. Emedicine 2012; http://emedicine.medscape.com/article/1098029 [Last updated on 2012, May 31]. |
|16.||Yamaoka H, Saski H, Yamasaki H, Oqawa K, Ohta T, Furuta H, et al. Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy. Diabetes Care 2010; 33 :150-155. |
|17.||Rademecker RP, Scheen AJ. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues. Diabetes Metab Res Rev 2007; 23 :348-355. |
|18.||Olasode OA. Why vitiligo in diabetes? Egypt Dermatol Online J 2005; 1 :1-6. |
|19.||Morgan AJ, Schwartz RA. Diabetic dermopathy: a subtle sign with grave implications. J Am Acad Dermatol 2008; 58 :447-451. |
|20.||Lopez PR, Leicht S, Sigmon JR, Stigall L. Bullosis diabeticorum associated with a prediabetic state. South Med J 2009; 102 :643-644. |
|21.||Rasi A, Soltani-Arabshahi R, Shahbazi N. Skin tag as a cutaneous marker for impaired carbohydrate metabolism: A case-control study. Int J Dermatol 2007; 46 :1155-1159. |
|22.||Mahmood T, Bari A, Agha H. Cutaneous manifestations of diabetes mellitus. J Pak Assoc Dermatol 2005; 15 :227-232. |
|23.||Ngo BT, Hayes KD, DiMiao DJ, Srinivasan SK, Hueter CJ, Rendell MS, et al. Manifestations of cutaneous diabetic microangiopathy. Am J Clin Dermatol 2005; 6 :225-237. |
|24.||Avci O, Caliskan S, Caliskan M. Erythema measurements may allow early diagnosis of diabetes mellitus in adult psoriatics. J Eur Acad Dermatol Venereol 2003; 17 :280-284. |
|25.||Ragunatha S, Anitha B, Inamadar AC, Palit A, Devamani SS. Cutaneous disorders in 500 diabetic patients attending diabetic clinic. Indian J Dermatol 2011; 56 :160-164. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]