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A 61-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 9 months and was also taking tramadol for diabetic peripheral neuropathy.
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
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. 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. Epidemiologic evidences have confirmed the correlation
between diabetes and the increased risk of different types of cancers. 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.
The patient presented with generalized body pain and gradual progressive numbness
was diagnosed with a rare disorder, paraneoplastic neurological syndrome.
Patient’s symptoms were significantly reduced with radiotherapy and
chemotherapy.
The patient had a
1-year history of type 2 diabetes. Medication for diabetes included 500 mg
metformin two times a day and 2.0 mg glibenclamide two times a day for ~9
months.
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.
|
Blood exam/Parameter |
Result/Unit |
Normal Range |
|
Fasting
glucose |
11.7
mmol/l |
3.9–6.1
mmol/l |
|
Glycated
hemoglobin (HbA1c), |
9.7% |
3.0–6.3% |
|
Serum
albumin |
28
g/l |
34.0–48.0
g/l |
|
Total
protein |
58
g/l |
60.0–83.0
g/l |
|
Erythrocyte
sedimentation rate (ESR) |
52
mm/h |
0.00–15.0
mm/h |
|
C-reactive
protein |
16.4
mg/l |
0.0–8.2
mg/l |
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. 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.
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.
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.
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.
Oncol Lett. 2015 Dec; 10(6): 3850–3852.
Painful neuropathy in a diabetic patient resulting from lung cancer and not diabetes: A case report
He-Bin Yao et al.
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