Painful neuropathy in a diabetic patient resulting from lung cancer
A 65-year-old man with a known history of diabetes mellitus, coronary heart disease, hypertension and pulmonary fibrosis was shown to a pain clinic. He complained of full-body pain, numbness and feelings of the pins and needles all over the body. He was on antidiabetic medication (500 mg metformin and 2.0 mg glibenclamide / twice a day) for the past 11 months and was also taking tramadol for diabetic peripheral neuropathy, but in vain. An experimental treatment with prednisone acetate (10 mg / day) for four days did not improve the symptoms. Almost two months ago, a chest computed tomography revealed the signs of pulmonary fibrosis. The severity of symptoms and pain worsened with time and showed 10/10 pain score. With these severe symptoms, the patient experienced disturbance in sleeping and lost 7 kg weight.
The most likely diagnosis of this presentation is
- Peripheral Diabetic Neuropathy
- Pulmonary Fibrosis
- Lung Cancer
- Paraneoplastic Neurological Syndrome (PNS)
Diabetes is one of the growing potential epidemics in India with > 62 million confirmed cases. In the beginning of the last decade, India topped the world with the highest number of diabetes patients (31.7 million) followed by China (20.8 million) and the United States (17.7 million). The prevalence of diabetes is predicted to be 366 million by 2030, up to 79.4 million individuals from India.1 Diabetic peripheral neuropathy is a frequent complication of diabetes affecting approximately 20% of patients with type 2 diabetes and 5% of those with type 1. Peripheral neuropathy is characterized by symmetrical pain, sensory abnormalities, increased sensitivity to pain and numbness originating from the distal end of the lower limb. It is important to rule out the other causes of these symptoms other than diabetes before confirming the diagnosis of peripheral diabetic neuropathy. 2 Epidemiologic evidences have confirmed the correlation between diabetes and the increased risk of different types of cancers.3 In this case, a rare case of lung cancer that presented with paraneoplastic neurological syndrome (PNS) was initially misunderstood as a case of diabetic peripheral neuropathy.
Upon visiting, the severity of pain was scoring 10/10, suggesting the unbearable pain experienced by the patient. Physical examination and general observation revealed the presence of skin rashes on the patient’s back. A neurological examination showed decreased bilateral tendon reflexes and the negative bilateral Babinski signs. The blood sample was assessed to look for the serum creatine kinase, creatine kinase-MB, full blood count and renal, hepatic and autoimmune profiles and revealed normal reports. However, some additional blood exam reports are presented in Table 1. Other examinations, including cardiac, respiratory, abdominal and musculoskeletal were normal.
The treatment was aimed to achieve a healthy blood glucose level, improving microcirculation, and to reduce the severity of the symptoms. Upon presentation, massage was given which found to relieve the pain. Since the initial diagnosis suggested peripheral diabetic neuropathy, the patient was treated for hyperglycemia. Approach included a biosynthetic human insulin (subcutaneous injection; before meals), and isophane protamine biosynthetic human insulin injection (before bed). To relieve the pain, thioctic acid (injection 0.6 g once a day for 7 days) and pain relievers (200 mg carbamazepine/ day and 100 mg tramadol/ twice a day for 10 days) were given. However, this approach failed to achieve the desirable symptom relief. The paradoxical phenomenon of severe symptoms and a lack of any detectable cause suggested that the pain may not be caused by the diabetes, and thus additional diagnosis was warranted. An additional CT scan of the chest revealed an enlarged node in the lower right lung. Although the invasive examinations like a lymph node biopsy was not performed, the patient was diagnosed with sensory neuropathy resulting from PNS. Therefore, six months of chemotherapy and radiotherapy were undertaken, that shown to relieve the symptoms. However, only carbamazepine was reported to relieve the patient's pain during the further follow-ups and visits.
In the present study of an old man with diabetes, experiencing numbness and pain over the whole body, the initial diagnosis was mimicked as a diabetic peripheral neuropathy. The symptoms symptoms were persisted even after receiving the treatment, suggesting the need of further diagnosis. Also, the typical signs of diabetic neuropathy, including hyperalgesia and allodynia also the typical signs of diabetic retinopathy or nephropathy were not reported. Therefore, the diagnosis of diabetic neuropathy was not supported. On further evaluation, chest CT scan and positron emission tomography-computed tomography scans confirmed the diagnosis of lung cancer with a tumor-node-metastasis stage of T1N3Mx. Treatment with chemotherapy and radiotherapy for six months showed significant improvement in the symptoms. To summarize, this was actually case of a paraneoplastic neurological syndrome (PNS) that presented as painful neuropathy resulting from lung cancer.
According to a recent international study, diabetes control in individuals worsened with longer duration of the disease with neuropathy the most common complication followed by cardiovascular complications, nephropathy, retinopathy and diabetic foot.1 Diabetic peripheral neuropathy is associated with abnormal ganglion cell complex focal loss volumeat the macula, which is independent of diabetic retinopathy, age, sex, type of diabetes, duration of diabetes and HbA1c levels. 4
Epidemiological studies have proven the association between type 2 diabetes and cancer. The underlying physiology may be attributed to insulin resistance and hyperinsulinemia which are the prominent indicators of type 2 diabetes. Hyperinsulinemia may cause cancer by imposing the effects of insulin on its cognate receptor and the insulin-like growth factor system.Antidiabetic medications for type 2 diabetes may also affect cancer cells directly or indirectly by altering serum insulin levels.5
Cumulative evidences have shown the approximately 21% of prevalence of the painful diabetic neuropathy (PDN) and the symptoms are more prevalent in patients with type 2 diabetes. Symmetrical lower limb paresthesiae, dysesthesiae, lancinating pains and allodynia, with nocturnal exacerbation and significant sleep disturbance are the indicators of PDN. Apart from peripheral and central alterations, metabolic alterations including increased glycemic flux and elevated plasma methylglyoxal levels have been implicated in the pathogenesis of PDN.6
In this patient, the lung cancer was confirmed after two months of occurrence of the typical symptoms of the paraneoplastic sensory neuropathy. PNS was diagnosed based on the diagnostic criteria established for the disease by an international panel of neurologists
It is important to look for other underlying causes other than diabetic complications in diabetic patients who experience neurological symptoms. It is particularly warranted when there are non-typical features, such as generalized pain.
1. Kaveeshwar SA and Cornwall J. The current state of diabetes mellitus in India. Australas Med J. 2014; 7(1): 45–48.
2. Yao HB, Chen YN, Shang J, Han QJ. Painful neuropathy in a diabetic patient resulting from lung cancer and not diabetes: A case report. Oncol Lett. 2015 Dec;10(6):3850-3852.
3. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, et al. Diabetes and Cancer. A consensus report. Diabetes Care. 2010 Jul; 33(7): 1674–1685.
4. Srinivasan S, Pritchard N, Sampson GP, Edwards K, Vagenas D, Russell AW, et al. Focal loss volume of ganglion cell complex in diabetic neuropathy. Clin Exp Optom. 2016 Mar 29. doi: 10.1111/cxo.12379.
5. Cannata D, Fierz Y, Vijayakumar A, LeRoith D. Type 2 diabetes and cancer: what is the connection? Mt Sinai J Med. 2010 Mar-Apr;77(2):197-213.
6. Basit A, Basit KA, Fawwad A, Shaheen F, Fatima N, Petropoulos IN, et al. Vitamin D for the treatment of painful diabetic neuropathy. BMJ Open Diabetes Res Care. 2016 Feb 10;4(1):e000148.