Archives of Academic Emergency Medicine. 2022; 10(1): e68 CA S E RE P O RT Hamman’s Syndrome Accompanied by Diabetic Ketoaci- dosis; a Case Report Koya Yamashita1, Takashi Hongo1, Tsuyoshi Nojima1, Tetsuya Yumoto1∗, Atsunori Nakao1, Hiromichi Naito1 1. Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. Received: June 2022; Accepted: July 2022; Published online: 21 August 2022 Abstract: Hamman’s syndrome is an uncommon clinical entity characterized by an idiopathic spontaneous pneumome- diastinum as a result of a sudden increase in intra-alveolar pressure. It can be triggered by repeated vomiting or Kussmaul breathing associated with diabetic ketoacidosis (DKA). Careful attention to this particular condition is needed to avoid under-diagnosis and to provide optimal management. Herein, we report a case of an 18-year- old man complaining of chest discomfort and progressive weight loss, ultimately diagnosed with Hamman’s syndrome secondary to DKA. The patient’s symptoms disappeared after intravenous fluid and insulin admin- istration, while his pneumomediastinum resolved following conservative treatment. Our report highlights the importance of recognition of the links between pneumomediastinum as a cause of chest pain in patients with DKA. Keywords: Hamman’s syndrome; Diabetic ketoacidosis; Mediastinal Emphysema Cite this article as: Yamashita K, Hongo T, Nojima T, Yumoto T, Nakao A, Naito H. Hamman’s Syndrome Accompanied by Diabetic Ketoaci- dosis; a Case Report. Arch Acad Emerg Med. 2022; 10(1): e68. https://doi.org/10.22037/aaem.v10i1.1709. 1. Introduction Hamman’s syndrome, a spontaneous pneumomediastinum and pneumopericardium, accompanied by diabetic ketoaci- dosis (DKA), is a rare clinical entity (1). Although the patho- genesis of Hamman’s syndrome caused by DKA is multifac- torial, intra-alveolar pressure can be increased by Kussmaul breathing or repeated vomiting, which may lead to alveolar rupture (2,3). The vulnerability of alveolar walls due to mal- nutrition may influence the development of pneumomedi- astinum (3). Lack of knowledge about Hamman’s syndrome secondary to DKA may lead to underdiagnose or unneces- sary workups and surgical treatment (3,4). Herein, we report an 18-year-old man who was diagnosed with Hamman’s syn- drome accompanied by DKA. We share our experience and a literature review on etiology and pathogenesis to increase familiarity with this syndrome among physicians. Physicians should be aware of the possibility that pneumomediastinum ∗Corresponding Author: Tetsuya Yumoto; Department of Emergency, Crit- ical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8588, Japan. Phone: +81-86-235-7426, FAX: +81-86-235-7427, E-mail: tyumoto@cc.okayama-u.ac.jp, ORCID: https://orcid.org/0000-0003- 1766-8026. can be induced by DKA associated with type I diabetes melli- tus. 2. Case presentation An 18-year-old man, a college student with no medical his- tory, came to the emergency department with two days of chest discomfort and history of marked body weight loss of 10 kg in two months. He did not take sugar-sweetened soft drinks daily. The patient reported polyuria and general fa- tigue for one week prior to admission. His height and weight were 165.0 cm and 63.9 kg, respec- tively. The patients’ vital signs were as follows: blood pres- sure 153/104 mmHg, heart rate 121 beats/minute, and res- piratory rate of 26 breaths/minute. He had no cold sweat- ing, no pallor, and no cyanosis. On physical examination, his chest was clear on auscultation with normal heart sound, and without chest wall tenderness on his abdomen. Subcu- taneous emphysema was not observed. He was severely de- hydrated with poor skin turgor and marked delay in capillary refill >2s. Significant laboratory results included a blood pH of 7.055, a blood glucose level of 901 mg/dL, white blood cells (WBC) 20,320 cells/µL, hemoglobin 16.2 g/dL, hemoglobin A1c 18%, serum potassium level of 6.1 mmol/L, blood urea nitrogen 20.6 mg/dL, and serum creatinine 0.93 mg/dL, Anti- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem K. Yamashita et al. 2 insulin, anti-islet antigen-2, and anti- glutamic acid decar- boxylase antibody tests were negative. Ketone bodies in his serum and urine were strongly positive. The other laboratory test results were unremarkable. Chest X-ray revealed pneumomediastinum and supraclav- icular subcutaneous emphysema without pneumothorax. A chest computed tomography (CT) revealed a few air bubbles inpneumomediastinum without pneumothorax or esophageal rupture (Figure 1A). No abnormal findings were noted in in the trachea, bronchi, or lung parenchyma. The patient was diagnosed with DKA associated with type I diabetes mellitus and pneumomediastinum. It was not known that our patient was diabetic until DKA and pneumo- mediastinum were found. The patient was admitted to the intensive care unit for glycemic control, and hydration with normal saline and an intravenous regular insulin infusion were initiated. Intra- venous insulin was transitioned to a subcutaneous insulin regimen within 24 hours of initiation due to improvement of glycemic control and the recalcitrant acidosis. We arranged a consultation with a diabetologist to review and control the disease. The pneumomediastinum was treated conservatively. His chest discomfort disappeared and chest X-ray showed no signs of worsening amount of gas in the neck and medi- astinum on day 2 of hospitalization. Following resolution of DKA, CT scan showed that the pneu- momediastinum had disappeared on day 12 of hospitaliza- tion (Figure 1B). He was discharged from the hospital on day 13 with an appointment for diabetic follow-up, including a chest radiograph. Since his discharge from hospital, he has not experienced a recurrence of pneumomediastinum during the one-month follow-up, having fully recovered with adequate education regarding the management of insulin at home. 3. Discussion The average age of Hamman’s syndrome patients with DKA is 20 years old. The average time period since diagnosis of diabetes mellitus is 7.2 years with average blood glucose levels of 638 mg/dl on presentation (2). Pneumomediastinum is rare and happens when air leaks into the connective tissue and finally enters the mediastinal space into the chest cavity from the bowel, airways, or lungs. It can result from physical trauma or other events including mechanical ventilation, esophageal perforation, hyperemesis, dental extraction, and obstetric delivery. These conditions sometimes become very severe and fatal. Al- though rare, pneumomediastinum accompanied by DKA is a benign, self-limiting condition (2). In general, patients with pneumomediastinum usually Figure 1: Chest computed tomography (CT) scan on admission demonstrated pneumopericardium (white arrow) and pneumome- diastinum (arrowhead) (A). CT showed that pneumomediastinum disappeared on day 12 of hospitalization (B). manifest extreme pain in the central chest. Other symptoms include voice distortion, labored breathing, and subcuta- neous emphysema, specifically affecting the chest, neck, and face. However, most of the clinical signs of pneumomedi- astinum complicated with DKA are likely to have subsided by the time metabolic control has been achieved (2). Since the symptoms of pneumomediastinum caused by esophageal rupture are similar to those of DKA with pneumomedi- astinum, the exclusion of esophageal rupture, which has a high mortality rate, is the primary task in the diagnosis of DKA complicated by pneumomediastinum (5). Of note, perforation of the esophagus due to increased intraluminal pressures following violent vomiting is sometimes seen in DKA (1,6). The precise pathophysiology of pneumomediastinum asso- ciated with DKA remains to be explained. Mainly, Kussmaul breathing, the compensatory respiratory mechanism in metabolic acidosis, raises alveolar pressure, predisposing the alveoli to rupture. DKA is often linked to severe vomit- ing caused by acidosis, which also increases intrathoracic pressures. Gastroparesis accompanied by diabetic mellitus may exacerbate vomiting. Our patient presented tachypnea, which may have been caused by increased expiratory efforts related to acidosis and ketotic hyperventilation. However, our patient did not complain of vomiting. Hu et al. recently reported that fibrotic changes in the lungs of individuals with poorly-controlled diabetes predispose the alveoli to rupture at lower intrathoracic pressures (7). In addition, diabetic malnutrition may influence lung mechanics by increasing surface forces and decreasing tissue elasticity (8). A previous experimental study indicated that starvation resulted in decreased surface density of lamellar bodies and mitochondria in a rat model (8). Although speculative, all This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2022; 10(1): e68 these phenomena might be involved in the development of Hamman’s syndrome. Of interest, there is a slight predominance of male patients with Hamman’s syndrome (71%) due to men’s greater av- erage muscle mass and their ability to create intrathoracic pressures higher than those of women (2). Pneumomediastinum can be diagnosed based on chest radiography. Chest CT is required to see mediastinitis or esophageal rupture. Conservative management is required with follow-up. Drainage of subcutaneous air or skin incisions may be needed in symptomatic patients with respiratory distress. Gastroesophageal endoscopy is only indicated when other pathologies are being considered (6). In general, Hamman’s syndrome is a benign entity with good prognosis. This case had several important points worth discussing. We reached an early diagnosis using non-invasive and inexpen- sive examinations by avoiding gastroesophageal endoscopy and/or surgical interventions. The clinical symptoms im- proved spontaneously after the intensive intravenous insulin therapies without invasive management. However, this disorder can have significant mortality if misdiagnosed or mistreated, which is almost 100% without insulin therapy (9). Our report highlights the importance of recognition and management of pneumomediastinum induced by DKA associated with type I diabetes mellitus. 4. Conclusion Emergency physicians should be aware of the possibility that pneumomediastinum can be induced by DKA associ- ated with type I diabetes mellitus. 5. Declarations 5.1. Acknowledgments None. 5.2. Authors’ contributions All authors met the criteria for authorship based on the Inter- national Committee of Medical Journal Editors’ recommen- dations. 5.3. Consent for publication Written informed consent was obtained from the patient for the publication of this case report and the accompanying im- ages. A copy of the consent form is available for review by the Editor-in-Chief of this journal. 5.4. Funding and supports There is no funding to declare. 5.5. Competing interests The authors declare that they have no competing interests. 5.6. Data availability The data used and/or analyzed during the current study are available from the corresponding author upon reasonable re- quest. References 1. Alkhuja S, Gazizov N, Charles G. Pneumomediastinum Complicating Diabetic Ketoacidosis and Boerhaave’s Syn- drome. Case Rep Med. 2013;2013:598720. 2. Pooyan P, Puruckherr M, Summers JA, Byrd RP, Roy TM. Pneumomediastinum, pneumopericardium, and epidural pneumatosis in DKA. Journal of Diabetes and its Compli- cations. 2004;18(4):242-7. 3. Gill I, Edhi AI, Cappell MS. Proposed characterization of the syndrome of epidural pneumatosis (pneumorrhachis) in patients with forceful vomiting from diabetic ketoaci- dosis as a clinico-radiologic pentad based on systematic literature review an illustrative case report. Medicine (Bal- timore). 2020;99(35):e21001. 4. Hayashi H, Nagao N, Yamazaki K, Asai R, Tanaka C, Kawai M. Spontaneous esophageal rupture managed with endo- scopic closure using an over-the-scope clip: A case report. Int J Surg Case Rep. 2021 Mar;80:105691. 5. Pain AR, Pomroy J, Benjamin A. Hamman’s syndrome in diabetic ketoacidosis. Endocrinol Diabetes Metab Case Rep. 2017;17-0135. 6. Pauw RG, van der Werf TS, van Dullemen HM, Dullaart RP. Mediastinal emphysema complicating diabetic ketoaci- dosis: plea for conservative diagnostic approach. Neth J Med. 2007;65(10):368-71. 7. Hu Y, Ma Z, Guo Z, Zhao F, Wang Y, Cai L, et al. Type 1 Diabetes Mellitus is an Independent Risk Factor for Pulmonary Fibrosis. Cell Biochemistry and Biophysics. 2014;70(2):1385-91. 8. Sahebjami H, Vassallo CL, Wirman JA. Lung mechanics and ultrastructure in prolonged starvation. Am Rev Respir Dis. 1978;117(1):77-83. 9. Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am. 1995;79(1):9–37. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Case presentation Discussion Conclusion Declarations References