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Presoon Kuruvilla Department of Internal Medicine, Caritas Hospital, Kerala, India

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Angel John Department of Internal Medicine, Caritas Hospital, Kerala, India

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Ashith Murali Department of Internal Medicine, Caritas Hospital, Kerala, India

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Summary

Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes. Insulin autoantibodies are diagnostic for the condition. Hirata’s disease has been seen to be associated with other autoimmune conditions. Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology. Although autoimmunity plays a role in the pathogenesis of both the diseases, association between the two has not been reported till date. In our case, a 72-year-old Indian woman with vitiligo for the past 30 years presented with recurrent episodes of fasting hypoglycaemia. She was found to have very high levels of fasting insulin, C-peptide, and insulin antibody and was diagnosed with IAS. Thus, we conclude that the clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.

Learning points

  • Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes in which insulin plays a major role.

  • Insulin autoantibodies are diagnostic for IAS. The endocrine insulin and its autoantibodies play a major role in the pathogenesis of the disease.

  • Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology.

  • IAS and vitiligo are two diseases with autoimmune aetiology which has been seen to be associated with each other (the first case to be reported).

  • The clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.

  • On dealing with autoimmune diseases, we should also keep in mind about other diseases with autoimmune pathogenesis.

Open access
Debby Christiana Soemitha Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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Deshinta Putri Mulya Division of Allergy and Immunology, Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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Hemi Sinorita Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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Summary

Diabetes foot ulcer (DFU) is a common long-term complication of diabetes. Intractable chronic wounds to standard care of diabetic foot raise the question of whether other factors intervene in disease development. We report a case of a 54-year-old male patient who came to Sardjito General Hospital with leg pain and previous history of multiple debridement and amputation for DFU referred from a remote hospital yet no improvement was evident in the surrounding lesion following treatment. Consequently, a histopathological examination was carried out proving the presence of other aetiologic factors, vasculitis and panniculitis existing in the lesion. In this case, we report a rare type of causative factor of foot ulcers among diabetic patients. Vasculitis suspected for polyarteritis nodosa accompanied by panniculitis is considered in this patient. The treatment of choice is corticosteroids or immunosuppressants based on the clinical condition, contrary to usual wound care in DFU. Based on the evidence, clinicians need to consider other causes than only macrovascular complications in a diabetic patient with DFU that is intractable to standard wound care. In this patient, vasculitis may be considered in forming diabetic foot ulcers alongside macrovascular complications.

Learning points

  • A thorough examination is essential to rule out other processes in intractable DFU patients.

  • Prompt management based on proper diagnosis is crucial to prevent peripheral arterial disease complications.

  • Vasculitis and macrovascular complication are inseparable processes forming DFU in this patient.

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Najoua Rbiai Department of Diabetology and Endocrinology, Mohammed VI Hospital

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Ikram Mahroug Department of Diabetology and Endocrinology, Mohammed VI Hospital

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Nada Zizi Laboratory of Epidemiology, Clinical Research and Public Health
Department of Dermatology, Mohammed VI Hospital, Faculty of Medicine and Pharmacy, Mohamed Ist University, Oujda, Morocco

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Hanane Latrech Department of Diabetology and Endocrinology, Mohammed VI Hospital
Laboratory of Epidemiology, Clinical Research and Public Health

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Summary

Cushing’s disease or pituitary adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is considered a rare condition. It is caused by hypersecretion of the ACTH by a pituitary adenoma that ultimately induces endogenous hypercortisolism by stimulating the adrenal glands. It is responsible for significant morbidity and mortality. The clinical signs and symptoms of hypercortisolism are usually common and non-specific including obesity, moon face, hypertension, hirsutism and facial plethora. The association between Cushing’s disease and calcinosis cutis which is defined as dystrophic calcium deposition in the skin and subcutaneous tissues is extremely rare. To the best of our knowledge, it has never been described previously in humans, probably like a symptom or complication of chronic and severe hypercortisolism. In this paper, we report a case of a 30-year-old female diagnosed with Cushing’s disease and presented bilateral leg’s calcinosis cutis complicated with ulceration. The evolution was favorable and the complete cicatrization was obtained 12 months following the suppression of systemic glucocorticoid excess.

Learning points

  • Calcinosis cutis is common in autoimmune connective diseases. However, to our knowledge, it has never been reported in humans with Cushing’s disease.

  • Given the rarity of this association, the diagnostic approach to calcinosis cutis must exclude the other etiologies.

  • Calcinosis cutis is challenging to treat with no gold standard therapy. In our case, the use of the combination of colchicine and bisphosphonates does not significantly improve the patient’s outcomes. In fact, we suppose that without treating the endogenous hypercortisolism, the calcinosis cutis will not resolve.

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Ricaurte Crespo-Trevino Universidad de Monterrey, Monterrey, Mexico
Neuro-Ophthalmology of Texas, and Neuro-Eye Clinical Trials Inc., Houston, Texas, USA

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Jade Schiffman Neuro-Ophthalmology of Texas, and Neuro-Eye Clinical Trials Inc., Houston, Texas, USA

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Shoaib Ugradar Cedars-Sinai Medical Center, Los Angeles, California, USA

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Kimberly Cockerham Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA

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Raymond Douglas The Jules Stein Eye Institute University of California, Los Angeles, California, USA

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David de Leon-Garza Universidad de Monterrey, Monterrey, Mexico

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Rosa Tang Neuro-Ophthalmology of Texas, and Neuro-Eye Clinical Trials Inc., Houston, Texas, USA

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Summary

Thyroid dermopathy is an uncommon manifestation of thyroid disease that impairs the quality of life in certain cases. Currently, the available treatments offer limited results and a chance of recurrence. Teprotumumab, a novel medication that results in the regression of thyroid ophthalmopathy, may have similar effects on dermopathy. We describe four patients treated with teprotumumab for their thyroid ophthalmopathy who concomitantly had dermatopathy upon initiation of their infusions. Patients improved after two to three infusions and three out of the four patients have not suffered a recurrence.Teprotumumab is a monoclonal antibody (MAB) that attenuates an inflammatory response, resulting in decreased edema and tissue expansion. Given the similarities of their pathophysiology, we believe that the resolution of thyroid dermatopathy and regression of thyroid eye disease occurs via the same mechanism. We encourage further investigation utilizing teprotumumab for patients whose dermopathy is associated with impaired quality of life.

Learning points

  • Thyroid dermopathy (TD), an uncommon manifestation of thyroid disease, may occasionally impair function and quality of life.

  • There are only a few treatments for TD, with limited results and high rates of recurrence.

  • Teprotumumab is a Food and Drug Administration-approved medication used for thyroid eye disease (TED).

  • Our patients treated with teprotumumab for TED showed improvement of TD, which demonstrates its potential use for this condition.

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Nami Mohammadian Khonsari Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

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Benyamin Hakak-Zargar Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada

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Tessa Voth Department of Biomedical Physiology and Kinesiology, Faculty of Science, Simon Fraser University, Burnaby, British Columbia, Canada

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Shahab Noorian Department of Pediatrics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

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Summary

Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder (LSD) that results in the accumulation of sulfate esters which go on to cause neurological deterioration and mental delay, skin changes, and dysmorphism. The disease can be categorized into three subtypes based on the age of onset: neonatal, late infantile, or juvenile. Our patient is a 2.5-year-old girl, the only child of a healthy couple. Prior to the presentation of the disease, she had not been noted to have any previous health complications. The condition began at the age of 6 months with developmental regression and global hypotonia. Following thorough evaluation and testing, the patient was diagnosed with severe late infantile MSD, although some features, such as minimal mental deterioration, minimal dysmorphic facial features, and minimal organ enlargement, did not fully correlate with the diagnosis, since in cases of severe forms of the condition these features are almost always quite marked. The unexpected minimalism of some of the patient’s MSD signs in spite of the severity of her MSD condition made her case worth further studying.

Learning points:

  • Treating dermatologic signs and symptoms greatly eased our patient’s discomfort.

  • We would suggest the use of appropriate supportive treatment for symptom management regardless of the life expectancy of the patient.

  • As regards the diagnosis of MLD, given that in some cases the patient may present with irregular features of the condition, a genetic evaluation may be useful for accurate diagnosis.

  • If motor function impairment is followed by dermatologic involvement, as seen in our patient and in many cases in the literature, MSD must be considered, and additional tests should be done to rule it out.

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Agnieszka Łebkowska Department of Internal Medicine and Metabolic Diseases, Diabetology and Internal Medicine

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Anna Krentowska Department of Internal Medicine and Metabolic Diseases, Diabetology and Internal Medicine

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Agnieszka Adamska Department of Endocrinology, Diabetology and Internal Medicine

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Danuta Lipińska Department of Endocrinology, Diabetology and Internal Medicine

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Beata Piasecka Department of Endocrinology, Diabetology and Internal Medicine

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Otylia Kowal-Bielecka Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland

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Maria Górska Department of Endocrinology, Diabetology and Internal Medicine

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Robert K Semple Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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Irina Kowalska Department of Internal Medicine and Metabolic Diseases, Diabetology and Internal Medicine

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Summary

Type B insulin resistance syndrome (TBIR) is characterised by the rapid onset of severe insulin resistance due to circulating anti-insulin receptor antibodies (AIRAs). Widespread acanthosis nigricans is normally seen, and co-occurrence with other autoimmune diseases is common. We report a 27-year-old Caucasian man with psoriasis and connective tissue disease who presented with unexplained rapid weight loss, severe acanthosis nigricans, and hyperglycaemia punctuated by fasting hypoglycaemia. Severe insulin resistance was confirmed by hyperinsulinaemic euglycaemic clamping, and immunoprecipitation assay demonstrated AIRAs, confirming TBIR. Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted. Over three years of follow-up, metabolic control remained satisfactory on a regimen of metformin, hydroxychloroquine and methotrexate; however, psoriatic arthritis developed. This case illustrates TBIR as a rare but severe form of acquired insulin resistance and describes an effective multidisciplinary approach to treatment.

Learning points:

  • We describe an unusual case of type B insulin resistance syndrome (TBIR) in association with mixed connective tissue disease and psoriasis.

  • Clinical evidence of severe insulin resistance was corroborated by euglycaemic hyperinsulinaemic clamp, and anti-insulin receptor autoantibodies were confirmed by immunoprecipitation assay.

  • Treatment with metformin, hydroxychloroquine and methotrexate ameliorated extreme insulin resistance.

Open access
Silvia M Becerra-Bayona Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga – UNAB, Bucaramanga, Colombia

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Víctor Alfonso Solarte-David Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga – UNAB, Bucaramanga, Colombia

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Claudia L Sossa Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga – UNAB, Bucaramanga, Colombia
Banco Multitejidos y Centro de Terapias Avanzadas, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle – FOSCAL, Floridablanca, Colombia

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Ligia C Mateus Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle – FOSCAL, Floridablanca, Colombia

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Martha Villamil Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle – FOSCAL, Floridablanca, Colombia

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Jorge Pereira Banco Multitejidos y Centro de Terapias Avanzadas, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle – FOSCAL, Floridablanca, Colombia

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Martha L Arango-Rodríguez Banco Multitejidos y Centro de Terapias Avanzadas, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle – FOSCAL, Floridablanca, Colombia

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Summary

Diabetic foot ulcer morbidity and mortality are dramatically increasing worldwide, reinforcing the urgency to propose more effective interventions to treat such a devastating condition. Previously, using a diabetic mouse model, we demonstrated that administration of bone marrow mesenchymal stem cells derivatives is more effective than the use of bone marrow mesenchymal stem cells alone. Here, we used the aforementioned treatments on three patients with grade 2 diabetic foot ulcers and assessed their beneficial effects, relative to the conventional approach. In the present study, two doses of cell derivatives, one dose of mesenchymal stem cells or one dose of vehicle (saline solution with 5% of human albumin), were intradermally injected around wounds. Wound healing process and changes on re-epithelialization were macroscopically evaluated until complete closure of the ulcers. All ulcers were simultaneously treated with conventional treatment (PolyMen® dressing). Patients treated with either cell derivatives or mesenchymal stem cells achieved higher percentages of wound closure in shorter times, relative to the patient treated with the conventional treatment. The cell derivative and mesenchymal stem cells approaches resulted in complete wound closure and enhanced skin regeneration at some point between days 35 and 42, although no differences between these two treatments were observed. Moreover, wounds treated with the conventional treatment healed after 161 days. Intradermal administration of cell derivatives improved wound healing to a similar extent as mesenchymal stem cells. Thus, our results suggest that mesenchymal stem cell derivatives may serve as a novel and potential therapeutic approach to treat diabetic foot ulcers.

Learning points:

  • In diabetic mouse models, the administration of mesenchymal stem cells derivatives have been demonstrated to be more effective than the use of marrow mesenchymal stem cells alone.

  • Mesenchymal stem cells have been explored as an attractive therapeutic option to treat non-healing ulcers.

  • Mesenchymal stem cells derivatives accelerate the re-epithelialization on diabetic foot ulcers.

Open access
Yael Lefkovits Wolfson Diabetes Centre, Addenbrooke’s Hospital Cambridge, Cambridge, UK

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Amanda Adler Wolfson Diabetes Centre, Addenbrooke’s Hospital Cambridge, Cambridge, UK

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Summary

Necrobiosis lipoidica diabeticorum (NLD) is a chronic granulomatous dermatitis generally involving the anterior aspect of the shin, that arises in 0.3–1.2% of patients with diabetes mellitus (). The lesions are often yellow or brown with telangiectatic plaque, a central area of atrophy and raised violaceous borders (). Similar to other conditions with a high risk of scarring including burns, stasis ulcers and lupus vulgaris, NLD provides a favourable environment for squamous cell carcinoma (SCC) formation (). A number of cases of SCC from NLD have been recorded (, , ); however, our search of the literature failed to identify any cases of either metastatic or fatal SCC which developed within an area of NLD. This article describes a patient with established type 1 diabetes mellitus who died from SCC which developed from an area of NLD present for over 10 years. Currently, there are a paucity of recommendations in the medical literature for screening people with NLD for the early diagnosis of SCC. We believe that clinicians should regard non-healing ulcers in the setting of NLD with a high index of clinical suspicion for SCC, and an early biopsy of such lesions should be recommended.

Learning points:

  • Non-healing, recalcitrant ulcers arising from necrobiosis lipoidica diabeticorum, which fail to heal by conservative measures, should be regarded with a high index of clinical suspicion for malignancy.

  • If squamous cell carcinoma is suspected, a biopsy should be performed as soon as possible to prevent metastatic spread, amputation or even death.

  • Our literature search failed to reveal specific recommendations for screening and follow-up of non-healing recalcitrant ulcers in the setting of necrobiosis lipoidica diabeticorum.

  • Further research is required in this field.

Open access
Anna Kopczak Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany
Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany

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Adrian-Minh Schumacher Institute for Stroke and Dementia Research

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Sandra Nischwitz Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany

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Tania Kümpfel Institute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians Universität LMU, Munich, Germany

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Günter K Stalla Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany

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Matthias K Auer Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany

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Summary

The autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE) gene. Immune deficiency, hypoparathyroidism and Addison’s disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD) antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS). The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3–4 times per day. GAD antibody-associated limbic encephalitis (LE) was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.

Learning points:

  • Episodic nausea cannot only be a sign of Addison’s disease, but can also be caused by epileptic seizures with gastrointestinal aura due to limbic encephalitis.

  • GAD antibodies are not only found in diabetes mellitus type 1, but they are also associated with autoimmune limbic encephalitis and can appear over time.

  • Limbic encephalitis can be another manifestation of autoimmune disease in patients with APECED/APS-1 that presents over the time course of the disease.

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Alessandro Mantovani Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Fabrizia Perrone Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Vincenzo Stoico Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Isabella Pichiri Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Laura Salvotelli Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Ilaria Teobaldi Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Massimiliano Bruti Division of Plastic Surgery, Department of Surgery

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Michela Conti Division of Infectious Disease, Department of Medicine and

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Luca Cima Division of Pathology Unit, Department of Diagnostics and Public Health, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Albino Eccher Division of Pathology Unit, Department of Diagnostics and Public Health, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

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Enzo Bonora Division of Endocrinology, Diabetes and Metabolism, Department of Medicine

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Summary

The incidences of type 2 diabetes mellitus and many cancers are rapidly increasing worldwide. Diabetes is a strong risk factor for some cancers (including lymphomas) and is also associated with adverse cancer outcomes. After gastrointestinal tract, the skin is the second most frequent extranodal site involved by non-Hodgkin lymphomas and the cutaneous B-cell lymphomas (CBCLs) range from 25% to 30% of all primary cutaneous lymphomas. The primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) is an aggressive lymphoma with a poor prognosis, representing roughly 20% of all primary CBCLs. Classically, the cutaneous manifestation of this lymphoma is a red or violaceous tumors arising on a leg. To date, despite the large body of evidence suggesting that diabetes is strongly associated with an increased risk of some cancers, very little information is available regarding a possible association between type 2 diabetes and primary cutaneous diffuse large B-cell lymphoma. In this report, we will present the case of a white adult patient with type 2 diabetes with chronic leg ulcers complicated by a primary cutaneous diffuse large B-cell lymphoma.

Learning points:

  • Diabetes mellitus is increasing worldwide as well as the incidence of many cancers.

  • Diabetes mellitus is a powerful risk factor for some cancers (including lymphomas) and is strongly associated with adverse cancer outcomes.

  • Seen that diabetes is strongly associated with an increased risk of cancers (including cutaneous lymphomas), clinicians should always keep in mind this complication in elderly patients with type 2 diabetes, even in a chronic leg ulcer with hypertrophy of the wound edge, which is hard to heal and does not have the typical characteristics of a diabetic or vascular ulcer. In these cases, a biopsy should be performed to rule out a neoplasm.

  • Early diagnosis and correct management of cancer in a patient with type 2 diabetes are crucial to improve clinical outcomes.

Open access