This is the first documented case of neuro-Sweet’s disease (NSD) in a 66-year-old Japanese woman with a 6 year history of myelodysplastic syndrome (MDS), who developed NSD in association with syndrome of inappropriate antidiuretic hormone secretion (SIADH) (Oka et al, 2017).
What is neuro-Sweet’s disease?
NSD is a rare neurological variant of Sweet’s syndrome (SS) that can affect the brain and spinal cord. Read more here.
What is syndrome of inappropriate antidiuretic hormone secretion?
SIADH is a relatively rare condition where the body makes too much of a hormone called antidiuretic hormone (ADH). ADH is produced in a part of the brain called the hypothalamus, and is then released by the pituitary gland at the base of the brain. ADH helps the kidneys to control the amount of water your body loses through the urine. In SIADH, the body retains too much water, leading to abnormally low levels of sodium in the blood (hyponatraemia). This happens as a result of the excess water diluting the blood and lowering the concentration of sodium.
What causes syndrome of inappropriate antidiuretic hormone secretion?
Common causes for SIADH include medication, hormone treatments, surgery under general anaesthesia, brain conditions, and lung disease. Rare causes include a disease of the hypothalamus or pituitary, cancer, and mental disorders.
A 66-year-old Japanese woman with a 6 year history of MDS, a blood cancer known to trigger SS, developed a fever and skin lesions in the form of a rash over both legs (Oka et al, 2017). A biopsy of a lesion showed lots of white blood cells called neutrophils in the tissues and no inflammation of the blood vessels. These findings were indicative of SS. The patient was given the oral steroid, prednisolone, which is the main form of treatment for SS, and this brought her symptoms under control.
The patient was readmitted to hospital 9 months later with a fever and reduced level of consciousness. Blood tests showed raised C-reactive protein (CRP), indicating increased levels of inflammation in the body. White blood cell count (WBC) was low and neutrophil count was borderline/low, despite being raised in most cases of SS (see ‘Additional notes’). No brain abnormalities were detected on MRI scan. Examination of cerebrospinal fluid (CSF), a clear and colourless fluid found in the brain and spinal cord, showed no neutrophils or white blood cells called lymphocytes, but raised protein levels. Bacterial or viral meningitis were suspected, and intravenous (via a drip in the vein) meropenem and acyclovir were commenced. However, the patient’s fever didn’t improve and her level of consciousness continued to deteriorate.
On day 10 in hospital, the patient was found to be negative for HLA-B51, but positive for HLA-B54. HLA-B51 is a genetic marker associated with a similar condition to SS called Behcet’s syndrome (see ‘Further information’), while HLA-B54 is associated with SS, particularly in Japanese patients (Sweet’s Syndrome UK, 2018). Due to neurological involvement, a diagnosis of NSD instead of SS was suggested (Oka et al, 2017). The intravenous steroid, methylprednisolone, was given. The patient’s condition improved and she was then started on prednisolone.
On day 30, the patient developed a fever and her level of consciousness deteriorated again. Tests revealed a low WBC and neutrophil count; CSF showed no lymphocytes or neutrophils, but raised protein levels; greatly elevated levels of interleukin 6 (IL-6) (see ‘Additional notes’); rapidly falling sodium levels in the blood; no kidney, adrenal or thyroid problems; MRI abnormalities – sagittal T1-weighted MRI showing an absence of high intensity signals in the posterior pituitary lobe. As a result of these findings, a diagnosis of SIADH was given, and the NSD was considered to be the most likely cause for this. Prednisolone and cyclosporine were commenced to treat the NSD, cyclosporine having being found to be useful in SS patients who have developed their condition secondary to low-risk MDS. A 3% sodium chloride intravenous infusion was given for the low sodium levels. The patient’s condition improved, and after discharge from hospital on day 70, she remained stable for a year and there was no recurrence of her symptoms.
Cytokines are proteins and molecular messengers and part of the body’s immune system. The overproduction or inappropriate production of cytokines, known as cytokine dysregulation, can result in disease. Cytokine dysregulation is a factor in SS, and the cytokine IL-6 plays a role in both NSD and SIADH (Oka et al, 2017). In this case, the patient’s IL-6 levels were greatly elevated, and this activates ADH secretion which can induce SIADH.
IN NSD, blood tests often show a raised WBC, including neutrophil count, and a raised CRP. CSF tends to show a slight increase in protein and an increase in the number of lymphocytes or neutrophils (Oka et al, 2017; Sweet’s Syndrome UK, 2018). However, MDS patients can sometimes have a lack of mature cells or neutrophils, and as a result, blood tests or CSF findings are less likely to clearly indicate NSD.
Newson, L. (2016) Hyponatraemia. Patient Info (online). Includes information on SIADH.
Ngan, V. (2002) Behcet Disease. DermNet NZ (online).
Oka, S., Ono, K. And Nohgawa, M. (2017) Successful Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Neuro-Sweet Disease in Myelodysplastic Syndrome. Internal Medicine (Tokyo, Japan), Dec 8th (J-Stage).
Sweet’s Syndrome UK (2018) Neuro-Sweet’s disease: a neurological variant (online).
2012-2018 Sweet’s Syndrome UK