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Open access

Ilaria Teobaldi, Vincenzo Stoico, Fabrizia Perrone, Massimiliano Bruti, Enzo Bonora and Alessandro Mantovani

Summary

Honey has been used as a wound dressing for hundreds of years by ancient civilizations, but only recently it has acquired scientific interest because of its relevant biological properties. In the last decade, indeed, several trials and observational studies have reported that, compared to conventional treatment (e.g. antiseptics, polyurethane film, paraffin gauze, soframycin-impregnated gauze), honey dressings seem to be better in healing time of different types of wounds, including diabetic foot ulcers. However, to date, information about a potential favorable biological effect of honey dressings on diabetic ulcers with exposed tendon are still scarce. Notably, foot or leg ulcers with exposed tendon are serious complications in patients with type 2 diabetes, as they are associated with an increased risk of adverse outcome. Therefore, the use of effective and safe treatments to bring these lesions to timely healing is very important in clinical practice. We herein report the case of a Caucasian adult patient with type 2 diabetes presenting a chronic right posterior lower limb ulcer (Texas University Classification (TUC) 2D) with tendon exposure that was successfully treated with honey dressings (glucose oxidase (GOX) positive with peroxide activity) in addition to systemic antibiotic therapy, surgical toilette and skin graft. In our case, the use of honey dressing for treating exposed tendon tissue probably allowed the timely wound healing. Although further studies are required, such treatment may constitute part of the comprehensive management of diabetic wounds, including those with tendon exposure, and should be considered by clinicians in clinical practice.

Learning points:

  • Honey has been used as a wound dressing for hundreds of years, but only recently it has acquired scientific interest for its biological properties.

  • Several studies have documented that, compared to conventional dressings, honey seems to be better in healing time of different types of wounds, including diabetic foot ulcers.

  • Our case report is the first to highlight the importance to use honey dressings also for the treatment of ulcers with tendon exposure in patients with type 2 diabetes, suggesting that this kind of dressing should be considered by clinicians in clinical practice.

Open access

Kewan Hamid, Neha Dayalani, Muhammad Jabbar and Elna Saah

Summary

A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It caused a significant distress to the patient and the family with multiple missing days at school in addition to financial burden and emotional stress the child endured. When clinical picture was combined with laboratory finding of macrocytic anemia, a diagnosis of hypothyroidism was made. Although chronic abdominal pain in pediatric population is usually due to functional causes such as irritable bowel syndrome, abdominal migraine and functional abdominal pain. Hypothyroidism can have unusual presentation including abdominal pain. The literature on abdominal pain as the main presentation of thyroid disorder is limited. Pediatricians should exclude hypothyroidism in a patient who presents with chronic abdominal pain. Contrast to its treatment, clinical presentation of hypothyroidism can be diverse and challenging, leading to a delay in diagnosis and causing significant morbidity.

Learning points:

  • Hypothyroidism can have a wide range of clinical presentations that are often nonspecific, which can cause difficulty in diagnosis.

  • In pediatric patients presenting with chronic abdominal pain as only symptom, hypothyroidism should be considered by the pediatricians and ruled out.

  • In pediatric population, treatment of hypothyroidism varies depending on patients’ weight and age.

  • Delay in diagnosis of hypothyroidism can cause significant morbidity and distress in pediatrics population.

Open access

Ali A Zaied, Halis K Akturk, Richard W Joseph and Augustine S Lee

Summary

Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.

Learning points:

  • Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).

  • Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.

  • Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.

Open access

Takatoshi Anno, Hideaki Kaneto, Ryo Shigemoto, Fumiko Kawasaki, Yasuhiro Kawai, Noriyo Urata, Hirofumi Kawamoto, Kohei Kaku and Niro Okimoto

Summary

Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores.

Learning points:

  • It is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia.

  • Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in everyday clinical practice.

  • Herein, we reported similar 2 cases of hypoinsulinemic hypoglycemia without diabetes presumably triggered by severe liver injury.

  • In both cases, hypoglycemia was improved by glucose infusion, although their liver injury was not improved.

  • We should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly subjects with low body weight.

Open access

Carlos Tavares Bello, Emma van der Poest Clement and Richard Feelders

Summary

Cushing’s syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing’s syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing’s disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing’s syndrome.

Learning points:

  • Severe Cushing’s syndrome is not always caused by ectopic ACTH secretion.

  • Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.

  • Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.

  • Cushing’s syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.

  • Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing’s syndrome.

Open access

Gueorgui Dubrocq, Andrea Estrada, Shannon Kelly and Natella Rakhmanina

Summary

An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain. During the endocrine workup, suspicion for adrenal insufficiency prompted 24-h urine collection for free cortisol, which was found to be undetectable (below LLQ of 1.0 µg/L). This prompted further evaluation of the hypothalamic–pituitary axis (HPA) by standard dose adrenocorticotropic hormone (ACTH) stimulation test. A 250 µg cosyntropin stimulation test was performed and confirmed HPA axis suppression. Baseline cortisol level was <1 µg/dL and stimulated cortisol level at 30 min was 3.8 µg/dL. The patient was diagnosed with iatrogenic Cushing syndrome and suppression of HPA axis secondary to the drug interaction between ritonavir (RTV) and intra-articular triamcinolone injection. Following endocrine evaluation and workup, the patient was admitted for planned orthopaedic procedure including elective left hamstring lengthening, distal femoral osteotomy and patellar tendon advancement. Taking into consideration the diagnosis of iatrogenic Cushing syndrome, at the start of the surgical procedure, 100 mg IV stress dose of hydrocortisone followed by 50 mg hydrocortisone every 8 h for 24 h was administered. Stress dosing was discontinued 24 h after the procedure. Throughout the hospitalization and upon discharge, the patient continued his ART. From initial presentation, patient has remained clinically stable throughout surgery and postoperative period.

Learning points:

  • Drug–drug interaction between ritonavir and triamcinolone can cause Cushing syndrome.

  • Although triamcinolone has a half-life of 3 h, an intra-articular injection may be systematically absorbed for 3 weeks after injection, and adrenal suppression may last as long as 30 days.

  • Co-administration of ritonavir and corticosteroids may result in an increase of plasma levels of corticosteroids levels, as they are both eliminated by CYP3A metabolism, and this interaction has the potential to prolong the half-life of triamcinolone several fold.

  • No specific guidelines are available for the management of iatrogenic Cushing syndrome secondary to ritonavir and corticosteroids.

  • One treatment option includes replacing ritonavir with a non-protease inhibitor-based regimen.

  • Initiating hydrocortisone replacement therapy to prevent an adrenal crisis is also an alternate option.

Open access

Alessandro Mantovani, Fabrizia Perrone, Vincenzo Stoico, Isabella Pichiri, Laura Salvotelli, Ilaria Teobaldi, Massimiliano Bruti, Michela Conti, Luca Cima, Albino Eccher and Enzo Bonora

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

Han Soo Park, Su Kyoung Kwon and Ye Na Kim

Summary

Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves’ disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient’s dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment.

Learning points:

  • The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.

  • In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.

  • During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.

  • Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

Open access

Ling Zhu, Sueziani Binte Zainudin, Manish Kaushik, Li Yan Khor and Chiaw Ling Chng

Summary

Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy.

Learning points

  • Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.

  • Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.

  • Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.

  • This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.

  • Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

Open access

Alessandro Mantovani, Maddalena Trombetta, Chiara Imbriaco, Riccardo Rigolon, Lucia Mingolla, Federica Zamboni, Francesca Dal Molin, Dario Cioccoloni, Viola Sanga, Massimiliano Bruti, Enrico Brocco, Michela Conti, Giorgio Ravenna, Fabrizia Perrone, Vincenzo Stoico and Enzo Bonora

Summary

Vertebral osteomyelitis (or spondylodiscitis) is steadily increasing in Western countries and often results from hematogenous seeding, direct inoculation during spinal surgery, or contiguous spread from an infection in the adjacent soft tissue. We present the case of a 67-year-old white patient with type 2 diabetes who went to Hospital for high fever, back pain, and worsening of known infected ulcers in the left foot. Despite intravenous antibiotic treatment and surgical debridement of the foot infection, high fever and lower back pain continued. Bone biopsy and two consecutive blood cultures were positive for Staphylococcus aureus. A spinal magnetic resonance imaging (MRI) was performed, revealing serious osteomyelitis in L4 and L5 complicated by an epidural abscess. Contiguous or other distant focuses of infection were not identified. In this case, diabetic foot could be considered as a primary distant focus for vertebral osteomyelitis. Clinicians should consider vertebral osteomyelitis as a ‘possible’ diagnosis in patients with type 2 diabetes complicated by foot infection that is associated with fever and lower back pain.

Learning points

  • Vertebral osteomyelitis is increasing in Western countries, especially in patients with type 2 diabetes.

  • The primary focus of infection is the genitourinary tract followed by skin, soft tissue, endocarditis, bursitis, septic arthritis, and intravascular access.

  • Diabetic foot could be a rare primary focus of infection for vertebral osteomyelitis, and, however, vertebral osteomyelitis could be a serious, albeit rare, complication of diabetic foot.

  • Clinicians should keep in mind the many potential complications of diabetic foot ulcerations and consider vertebral osteomyelitis as a “possible” diagnosis in patients with type 2 diabetes and foot ulcers associated with nonspecific symptoms such as lower back pain.

  • Early diagnosis and correct management of vertebral osteomyelitis are crucial to improve clinical outcomes.