ABSTRACT
Objective:
To explore clinicopathological features and
prognosis of
antineutrophil cytoplasmic antibody (
ANCA)-associated
vasculitis (AAV) in
children induced by
antithyroid drugs.
Methods:
The clinicopathological features,
treatment and
prognosis of 3
children with AAV induced by
antithyroid drugs in the Department of Pediatric
Nephrology and
Rheumatology of the First Affiliated
Hospital of
Sun Yat-sen
University were analyzed retrospectively, and the
literatures were reviewed.
Results:
(1) Among the 3 cases, there were 2
females and 1
male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All
patients had medication
history of
propylthiouracil (PTU) and/or
methimazole (MMI) before onset. Initial manifestation was
pallor and renal involvements with nephrotic
proteinuria,
hematuria and renal function abnormality, while 2 of them had
hypertension. Extrarenal manifestations were also presented case 1 presented with
rash,
arthralgia and cardiac insufficiency; case 2 had
brain involvement with repeated convulsions; case 3 presented with
arthralgia and
lung involvement. They were all tested positive for
p-ANCA and MPO-
ANCA. Initial renal histopathology of the 3 cases were consistent with
ANCA-associated
glomerulonephritis, which were classified into
sclerosis, crescentic and mixed class respectively. After 8 months of
treatments, repeated renal
biopsy of case 3 had demonstrated progression to
sclerosis class.
Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the
children were all treated with
corticosteroid combined with intravenous
pulse cyclophosphamide therapy.
Plasma exchange was performed in case 2 and case 3 due to rapidly progressive
glomerulonephritis and
disease recurrence (suspected pulmonary
hemorrhage), respectively. Case 3 was treated with
rituximab combined with
mycophenolate mofetil after
recurrence. The extrarenal symptoms relieved quickly after
treatments in all cases.
P-ANCA and MPO-
ANCA became negative in case 1 and case 2 after 6 months of
treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively case 1 develop
chronic kidney disease (CKD) stage 2 with normal
urinalysis; case 2 develop CKD stage 5 and had
sudden death at home
at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic
proteinuria and microscopic
hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the
literature and 3 cases in this study. Symptoms of AAV appeared in
children after an average
administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone).
Kidney (28 cases, 93.3%) and
lung (12 cases, 40.0%) were commonly involved, while
brain (2 cases, 6.7%) was rarely involved. The pathological changes of
kidney were crescent
nephritis (5/23) and necrotizing pauci-
immune complex nephritis (11/23). The total remission rate was 93.3% (28/30) after
antithyroid drugs withdrawal and
treatment with
corticosteroids and
immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and
death. (3) Thirty cases were divided into complete response group ( n=19) and incomplete response group ( n=11) according to the
treatment response. Compared with complete response group, the proportions of massive
proteinuria (8/11 vs 5/19), fibrinoid
necrosis (7/9 vs 4/14), deposition of
immune complex in renal
tissues (6/9 vs 2/14) and
administration of
immunosuppressants (10/11 vs 5/19), and degree of tubular
atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05).
Conclusions:
PTU and MMI can both induce AAV in
children, and AAV may occur after
short-term course of
administration.
Kidney and
lung are commonly involved while
brain involvement is rarely seen. Timely withdrawal of
antithyroid drugs and proper
treatments with
corticosteroids and
immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range
proteinuria, renal fibrinoid
necrosis, immune-complex deposition and tubular
atrophy may be the
risk factors of AAV for poor
prognosis.