8 Yrs Boy Diagnosed with CIDP + Blood Disorder (Low Hb & Platelet)

My son, Sanjay Raao , 8 years old. He was an active child, playful with normal milestone development. He had suffered acute weakness of lower limbs in early January 2019; and currently suffering severe pancytopenia past 5 months.

<u>Clinical Summary</u>
1. Atypical chronic inflammatory demyelinating polyneuropathy (CIDP) – Diagnosed in
May 2019. Presented with recurrent peripheral neuropathy since January 2019. Transient improvement with IV Immunoglobulin infusions at presentation and at each recurrence.

He had the following episodes of neuropathy.

<u>January 2019</u>
Pre-morbidly Sanjay was a bright child with normal motor function for his age. He had an uneventful perinatal period other than a low birth weight of 1.6kg and is fully immunised.

In mid-January 2019, he was noted to have progressive lower limb weakness, unsteady gait and constipation. On examination he had distal motor weakness of the lower limbs and generalized loss of reflexes but no sensory or cranial nerve involvement. MRI spine showed enhanced nerve roots, but MRI brain was normal. Nerve conduction studies showed reduced conduction velocity of the right peroneal nerve and right sural nerve.

He was treated as possible Guillain Barre Syndrome and given course of IV Immunoglobulin 2g/kg over 2 days. Post immunoglobulin he regained some function and was able to ambulate with support and his constipation resolved.

<u>18 January 2019</u>

<u>MRI Thoracolumbar Spine</u>

No significant disc prolapse seen causing compression of the thecal sac/ spinal cord. Normal signal intensity of the imaged parts of the thoracic spinal cord. No obvious signal change,
enhancement or intramedullary mass lesion at the thoracic spinal cord and conus. Faint
enhancement of the descending nerves within the spinal canal at the lumbar spine level.
Possibility of Guillain- barre syndrome should be considered.

<u>18 January 2019</u>

<u>Ganglioside Autimmune Profile</u>
Autoimmune ganglioside- monosialic acid IgM & IgG: negative

<u>February 2019</u>
In mid-Feb 2019 about 3 weeks post first IV Immunoglobulin infusion, there was a recurrence of his lower limb weakness which was worse this time with an inability to ambulate. Again, the reflexes were absent with a repeat nerve conduction study shows reduced conduction velocities of all motor nerves (upper and lower limbs).

The second course of Immunoglobulin was administered on 24/2/12019 over 2 days. This time his recovery was better, and he was ambulating with one handheld and was generally doing well.

<u>March 2019</u>
3 weeks after the 2nd IVIG infusion, he had an episode of abnormal behavior associated with
spontaneous bruising lasting 2 weeks. He was still able to ambulate and hence his parents did
not seek any medical attention. These symptoms resolved about 2 to 3 weeks later in early April.
During this period, he also had a very poor oral intake with retching and lost 2kg of weight. In retrospect, it was suspected that he may have had some swallowing incoordination and delirium due to the underlying pathology. He still has intermittent retching till today depending on the character of food consumed and how quickly he eats.

<u>April2019</u>
In the 2nd week of April he developed the 3rd episode of lower limb weakness. Other than peripheral neuropathy, systemic examination was unremarkable. He was extensively investigated for possible systemic illness/ occult malignancy/ rheumatological disease. Other than the abnormal nerve conduction studies, highish ferritin, fluctuating platelet counts (never below 100) and hepatic transaminitis; all other investigations were negative.

He was then referred to a pediatric neurologist in Sunway Medical Centre, Kuala Lumpur, Malaysia specializing in peripheral neuropathy. In view of the waxing and waning nature of the disease with frequent relapses; the suspected diagnosis was atypical CIDP.

At the Sunway Medical Center, Kuala Lumpur, he was given IV Methylprednisolone followed by prednisolone tablet for 3 months in May 2019 after diagnosis of CIDP.  He made good progress subsequently was able to walk few steps without support.

Oral Azathioprine was planned at that time, but his parents were not keen to commence this treatment for fear of its adverse effects and at the same time he showed gradual neurological improvement with the intensive physiotherapy. He had no further relapse or deterioration since then.

Oral Azathioprine was started only in October 2020 after the parents agreed to it although at time there were no new or worsening neurological symptoms. They understood that the medication was not likely to reverse the neurological deficits but would slow down the progression of the disease.

<u>May 2021</u>

<u>Pancytopenia Likely Autoimmune Aetiology

</u>

Fever and symptomatic anemia in May 2021 and his blood count showed pancytopenia in a private hospital. Private pediatrician consulted Paeds neuro and Azathioprine was withheld
since May 2021. No transfusions were required at that time.

About 2 weeks later, the counts further dropped (10/6/2021   Hb:8.2, WBC:5.5, (ANC 0.2), Platelet: 40) and was treated expectantly.

<u>30 June 2021</u>
He presented to the general pediatric ward of Penang Government Hospital on 30th June 2021 with fever for 4 days, gum bleeding with easy bruising over the lower limbs and pallor for one month. Blood results showed pancytopenia. There was no weight loss or night sweats, new neurological or GIT symptoms. There was no obvious infective source of the fever and he had no sick contacts.

Full Blood Count (FBC) on admission (30/06/21) was:  Hb 5.7, TWCC 5 ( ANC l) and Plt : 25.
On examination, he was febrile but not septic.

He was started on IV Cefepime in view of his significant neutropenia.
Blood culture on admission grew Corynebacterium Jeikeium.
His repeated cultures were sterile thereafter.
There were no cardiac vegetations or intraabdominal collections on imaging.
Throughout his admission, he was transfused with packed cell and platelet in view of severe anemia and thrombocytopenia.

Besides that, he had recurrent spikes of temperature. He also appeared mildly tachypnoeic after pack cell transfusion.

 

As he developed dry cough, a diagnosis of atypical pneumonia was made, and he was given Clarithromycin which was subsequently withheld as the Mycoplasma serology was negative.

 

His first 2 Chest X-Ray was reported as worsening air space opacities in both lungs, suggestive of worsening pneumonia. The third Chest X-ray showed improvement. His fever subsequently resolved with 1 week of IV Cefepime.

Prior to this, he had no significant infections from early childhood to date. Since the diagnosis,
he had fluctuating temperature occasionally as high as 38.5°C with no obvious source of infection. His temperature instability was thought to be attributed to some degree of autonomic dysfunction leading to temperature dysregulation.

He was worked up for a possible autoimmune disorder during this admission and the results as before, were not suggestive.

<u>05 July 2021</u>
A bone marrow aspiration and trephine biopsy was done on 5th July 2021.
The aspirate was heavily diluted with peripheral blood, there were no indications of malignancy but there was an excess of lymphocytes.

Trephine biopsy also showed an excess of T lymphocytes. It was sent to Hospital Raja Permaisuri Bainun (HRPB Ipoh (another Government Hospital) for a second opinion by a lymphoma pathologist Dr Shafinaz. Malignancy was ruled out and the marrow appeared to have polyclonal proliferation of mature T Lymphocytes, likely reactive.

<u>Aug until Now (Oct 21)</u>
He is currently every 2 weekly blood transfusions.
The last packed cell/ platelet transfusion was done on 14th October 2021.

All investigations to date are inconclusive for autoimmune diseases.

Other Blood tests performed:
Epstein Barr Virus IgG VCA Positive (blood test done on 13/07/21).
Cytomegalovirus IgG Detected (blood test done on 13/07/2021).

Apart from severe anemia with thrombocytopenia, his fever persistently high at around 38.0°C to 39.5°C (100.4°F – 103.1°F), since May 2021.

Dear Doctor/team, I hope you could assist with your expertise to diagnose my son. We are still unsure of the diagnosis and the treating Hematologist unable to give any treatment.

Kindly help us.
Please reach me at saandilian@gmail.com and jamesrauo@yahoo.com
Thanks