|Year : 2019 | Volume
| Issue : 1 | Page : 38-41
Subcutaneous immunoglobulin in infantile chronic inflammatory demyelinating polyneuropathy: A case report
Paola Cianci1, Silvia Salvatore1, Alex Moretti1, Angela Berardinelli2, Alessandro Salvatoni1, Maddalena Marinoni1, Massimo Agosti1
1 Woman and Child Department, Ospedale “F. Del Ponte,” University of Insubria, Varese, Italy
2 IRCCS Mondino National Neusrological Foundation, Pavia, Italy
|Date of Web Publication||18-Jun-2019|
Dr. Paola Cianci
Woman and Child Department, Ospedale “F. Del Ponte,” University of Insubria, Via F. Del Ponte 19, 21100 Varese
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronically progressive or relapsing sensorimotor disorder presumably due to antibody-mediated reactions. It is a rare condition in children, with estimated prevalence as 0.48 per 100,000 among patients younger than 20 years of age. Recommended treatments include immune modulators, intravenous immunoglobulins (IVIgs), steroids, and plasmapheresis. Management of pediatric CIDP is challenging because of the lack of evidence-based efficacy of the current therapies in children. Because of the rarity of this condition, there are no double-blind randomized studies to support the therapeutic choice as well as to identify the optimal first-line therapeutic regimen. IVIgs are widely used but the intravenous administration is usually uncomfortable, especially for children. Subcutaneous immunoglobulins (SCIgs) have proven to be effective in adults with CIDP and in children affected by antibody deficiencies and other different immune and inflammatory disorders. Herein, we described the case of a 7-year-old boy, affected by CIDP who clinically responded to IVIg but was dependent on this therapy. In order to improve his quality of life, we switched to SCIg with excellent result.
Keywords: Children, CIDP, chronic inflammatory demyelinating polyneuropathy, intravenous immunoglobulins, subcutaneous immunoglobulins
|How to cite this article:|
Cianci P, Salvatore S, Moretti A, Berardinelli A, Salvatoni A, Marinoni M, Agosti M. Subcutaneous immunoglobulin in infantile chronic inflammatory demyelinating polyneuropathy: A case report. J Pediatr Neurosci 2019;14:38-41
|How to cite this URL:|
Cianci P, Salvatore S, Moretti A, Berardinelli A, Salvatoni A, Marinoni M, Agosti M. Subcutaneous immunoglobulin in infantile chronic inflammatory demyelinating polyneuropathy: A case report. J Pediatr Neurosci [serial online] 2019 [cited 2020 Jul 14];14:38-41. Available from: http://www.pediatricneurosciences.com/text.asp?2019/14/1/38/260612
| Introduction|| |
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic and treatable disorder of the peripheral nerves with clinical and immunological heterogeneity. Currently, the diagnosis of CIDP is based on clinical, laboratory, and electrophysiological criteria. CIDP has a remarkably heterogeneous clinical manifestation, with pure motor or sensory impairment or with distal, multifocal, or focal distributions, being unclear whether the typical and atypical phenotypes share the same pathogenesis. Moreover, despite various sets of diagnostic criteria, not all patients are yet identified, as there are reports of response to treatment in patients not fulfilling the current clinical and/or electrophysiological criteria. Classically, CIDP is characterized by hypo- or areflexia and progressive or relapsing motor and/or sensory dysfunction of more than one extremity, lasting at least 2 months. The presentation may be subacute or insidious, and the evolution be monophasic, progressive, or polyphasic with relapsing and remitting phases., Although the majority of patients shows a progressive or relapsing phase lasting more than 8 weeks, up to 16% of cases present an acute onset resembling Guillain–Barré syndrome (GBS). “Acute-onset CIDP” in a patient initially diagnosed as GBS is likely if deterioration continues longer than 2 months from onset or if at least three treatment-related fluctuations occur.
CIDP may occur from infancy to late adulthood with increasing disease prevalence with advancing age. The prevalence in adults has been reported as 1.0–1.9 per 100,000, whereas it is 0.48 per 100,000 among those younger than 20 years. Different sets of diagnostic criteria have been proposed in the recent years, with different sensitivity and specificity. The most accepted diagnostic criteria dated back to 2010 and include progressive symmetrical proximal weakness and hyporeflexia, and electrophysiological evidence of acquired demyelinization.
In CIDP, electrodiagnostic studies show a predominantly demyelinating polyneuropathy such as diminished motor conduction velocity, prolonged distal latencies, and prolonged or absent F waves; the cerebrospinal fluid (CSF) analysis commonly reveals elevated protein concentration and spine MRI demonstrates enhancement of nerve roots.
The pathophysiology of CIDP is not fully understood, but the existence of pathological and radiological evidence of inflammation in nerves and nerve roots, the pathogenetic role of immune cells, and particularly, the favorable response to immune therapies support an immune-mediated pathogenesis. Immunomodulatory therapy is the mainstay of treatment and includes intravenous immunoglobulins (IVIgs), steroids, and plasmapheresis.
In children, it is rare to switch from one clinical phenotype to a different one or to become resistant to a previous effective treatment. Treatment in children is based on what reported in randomized clinical trials performed in adults. There is no consensus for initial choice, nor for second-line therapies in patients unresponsive to IVIg and corticosteroids, nor for corticosteroid-dependent patients. IVIgs are used to treat various immunodeficiency syndromes and hematological, autoimmune, or immune-mediated diseases,, and are the preferred treatment at diagnosis of CIDP in adults., IVIgs are generally well tolerated, although adverse effects such as allergic reactions, thromboembolic complications, and headaches can occur. Besides, IVIgs are expensive and require monthly hospital admission. Subcutaneous immunoglobulins (SCIgs) have shown efficacy in adult patients with CIDP. They have also been used in different immunodeficiency and immune-mediated syndromes in children. The advantages of SCIg include reduction of school (and parental work) absenteeism, adverse systemic reactions, and a more constant serum immunoglobulin plateau. SCIgs have been considered in a cohort of adolescents and adult patients with CIDP. A large trial in adult population has recently shown that SCIgs were efficacious and well tolerated as maintenance treatment. Hitherto, no child successfully treated with SCIg has been described in the literature.
| Case Report|| |
A 35-month-old boy presented with a 2-month history of gradual bilateral limb weakness. He was born to healthy non-consanguineous parents, through vaginal delivery at 40 weeks of gestation. Weight, length, and head circumference at birth were 2940g (3–10 percentile), 49cm (10–25 percentile), and 34.5cm (25–50 percentile), respectively. Pregnancy was uneventful and Apgar scores at the first and fifth minute were 9 and 10, respectively. His cognitive, communicative, and socio-emotional development milestones were regularly reached and he was able to walk independently at the age of 13 months. He always enjoyed good health up to 2 months before our first evaluation and, specifically, no infections were reported during the previous months. Family history was negative for neuromuscular, metabolic, congenital, or autoimmune diseases.
He showed a progressive distal muscle weakness with a severe ataxic gait, associated with fatigue, difficulty using stairs, and getting up from a sitting position. On physical examination, the muscular tone was reduced as well as the muscle bulk with a proximodistal progression in lower limbs. He demonstrated the Gowers’ sign and required additional external support to rise from the floor. Standing was possible only with enlarged base, and waddling gait and steppage were observed at first evaluation. Because of the young age, the cooperation of the child was poor and sensation could not be properly clinically evaluated. Deep tendon reflexes (DTR) were not evocable on both proximal and distal extremities. No other neurologic or neuromotor abnormalities were noticed. Normal bladder function was maintained; neither urinary problems nor infections were reported. Laboratory tests were performed. Full blood count, creatine phosphokinase (104 U/L), aminotransferase inflammatory markers (ESR, CRP), serum protein and electrophoresis, urea, electrolyte and creatinine, and urine analysis were all normal. Phosphatase alkaline was increased (842 U/L).
CSF analysis, spine MRI with contrast, and nerve conduction analyses were performed during the first week after our first clinical evaluation. On CSF analysis, protein concentration was increased (albumin 71mg/dL) whereas WBC was within normal limits (<2 cells/μL). Brain MRI showed no pathological findings, but spine MRI demonstrated symmetric smooth pial enhancement of the cauda equina. On nerve conduction study, prolonged motor conduction, low amplitude of compound muscle action potential, and slow conduction velocity were found in both legs; F-wave latencies were prolonged in median and ulnar nerves; sensory action potentials in the sural nerve was bilaterally prolonged and lower in amplitude. These findings suggested segmental demyelinating, mixing sensorimotor polyneuropathy combined with axonal involvement. The child was diagnosed with CIDP and received a 5-day course of IVIg (400mg/kg/day). He showed an immediate improvement of motor functions, walk speed, and balance; DTR were difficult to evocate. His strength and gait returned to normal after the first month of treatment and his motor skills further improved during the following weeks. He received IVIg treatment every 3 weeks at the same dose (400mg/kg/day for 5 days) for 7 months, then IVIg doses were gradually tapered until 250mg/kg once per month, but he relapsed, showing again excellent response to a full dose of IVIg. Each attempt to taper the IVIg dose or to increase the time window between two intravenous administrations was associated with symptom relapses; no clinical response was seen on steroids (prednisone 2mg/kg/day for 1 month). CSF analysis was not repeated after IVIg therapy; the spine MRI and nerve conduction studies were checked after 18 months since starting treatment and were reported as normal.
At 6 years, we decided to shift IVIg to SCIg, maintaining the dose of 2g/kg every 3 weeks (divided in to six administrations) achieving a clinical stabilization. Infusion site included lower abdomen region. The length of the needle used was 6mm. The duration of administration ranged from 60 to 120 mins depending on the dose (5g or 10g) of SCIg that was administered weekly. Signs of local reaction as minimal skin rashes occurred only during the first administrations. At the last evaluation, 2 years after starting SCIg, he did not show difficulty in walking, climbing stairs, and arising from the floor; he was able to jump and could walk on his heels. Neurologic examination showed normal DTR and muscular strength. No adverse effect was reported. Repeated nerve conduction studies, with 12-month intervals, were normal; no other follow-up analyses have been performed so far.
| Discussion|| |
Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks specific biomarkers to support the diagnosis.
Randomized controlled trials have shown IVIg, as well as plasma exchange and corticosteroids, as beneficial treatment in adults,,, although two-thirds of patients with CIDP need long-term therapy. Currently, IVIgs are commonly considered a first-line treatment particularly in children, largely because of more rapid clinical response and lower adverse effects compared to long-term use of steroids.
Immunoglobulin therapy can be tailored to suit individual needs choosing intravenous or subcutaneous administration in children with immune deficiency. Advantages and disadvantages of each route should be considered when selecting patient’s treatment. The intravenous route results in an early peak of IgG immediately after the infusion, followed by a slow decline in antibody levels during the following days. Adverse reactions may occur and include chills and fever, or, more rarely anaphylactic shock, thrombosis, or hemolysis. Moreover, IVIgs are expensive and require venous access and, so generally, a hospital admission every 3–4 weeks.
SCIgs have been used in different immunodeficiency syndromes in children. SCIgs are absorbed more slowly into the bloodstream via the lymphatic system and require more frequent (at least weekly) administrations compared to IVIg. Hence, a less variable steady-state IgG level is maintained, which eliminates the peaks and troughs that occur with monthly IVIg therapy.,
The dose of immunoglobulin used was 2g/kg, or equivalent, in our patient, to 45g every 3 weeks if used intravenously. As SCIg required more frequent administration compared to IVIg, we considered the dose of 15g weekly as SCIg. The commercial preparation available in Italy dosed 5 or 10g, and as he was the first case using SCIg we preferred to start with two administrations per week (one dosed 5g and the other dosed 10g).
SCIg can determine local, usually transient, side effects such as swelling, turgor, local inflammation, and itching., Patient education and training at the onset SCIg treatment is required, and a follow-up is necessary to ensure efficacy and patient safety. SCIgs are usually preferred by children and their families because of a better patient compliance, autonomy, and quality of life compared to IVIg. SCIgs are cost-saving, avoid hospital admissions, and reduce days of school and work absenteeism for patients and parents.
In adults with CIDP, SCIgs represent an alternative route of administration and case series reported clinical efficacy and safety.,, Only recently a large trial has reported efficacy, safety, and tolerability of weekly SCIg, suggesting them as a possible maintenance therapy for this condition; however, no young children were recruited.
Our report showed that SCIgs could be considered as a therapeutic choice also in pediatric CIDP. In our case, the maintenance dose of 2g/kg every 3 weeks was associated to long-term clinical efficacy and appeared to prevent the relapse of the disease for at least 24 months. However, efficacy, safety, and tolerability of SCIg must be confirmed in a large pediatric population, and future clinical trials are necessary to define the optimal therapeutic regimen of SCIg in CIDP.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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