Goodpasture’s syndrome (GPS) remains a very rare disease entity in the pediatric population characterized by the presence of pulmonary hemorrhage and rapidly evolving glomerulonephritis. We hereby describe the case of a 2-year-old girl who presented with renal failure and was diagnosed with GPS. A brief review of the literature in regard to data on demographics, pathogenesis, clinical features, diagnosis, treatment, and prognosis for renal recovery is also provided.
Goodpasture’s syndrome (GPS) is a rare and life threatening autoimmune condition with autoantibodies directed against the glomerular basement membrane (GBM) antigen. The term GPS refers to the triad of pulmonary hemorrhage, glomerulonephritis, and anti-GBM antibodies while Goodpasture’s disease (GD) is the preferred terminology in the absence of pulmonary hemorrhage [
A 2-year, 11-month-old Hispanic female presented to her primary care physician’s office with swelling of the hands and face following one week of fever, sore throat, and malaise. A screening urine analysis (U/A) revealed 3+ protein and blood with numerous red blood cells per high power field. Further work-up also demonstrated anemia (Hb of 8.5 g/dl) and several electrolyte imbalances with azotemia (BUN 116 mg/dl and Cr 7.3 g/dl) prompting immediate transfer to our Children’s Hospital for further evaluation and management.
On admission, examination revealed a pale child with bilateral mild pedal edema and blood pressure of 125/71 mm Hg. She was afebrile, mildly tachycardic, and saturating at 100% in room air and parents denied any h/o joint pain/swelling or skin rash. Her urine output was noted to be darker and less frequent over the past few days.
Past medical history was significant for an admission about 7 months back with respiratory distress and presumed pneumonia. Labs at that time were significant for severe anemia (Hb 6.9 g/dl) and iron deficiency. Initial chest X-ray showed bilateral diffuse peribronchial cuffing and nodular opacities with concerns for severe bronchiolitis/bronchopneumonia (Figure
Chest X-ray on initial presentation.
Work-up during this current admission confirmed anemia (Hb 7.8 g/dl) with a slightly elevated white blood cell count (10,400/mm3) and platelet count (234,000/mm3). Serum chemistry panel was abnormal for hyperkalemia (6 mmol/L), metabolic acidosis (Hco3 of 8 mmol/L), hypocalcemia (5.6 mg/dl), hyperphosphatemia (8.9 mg/dl), and renal failure (BUN 120 mg/dl and Cr 7.01 mg/dl). Further work-up involved evaluation as to identify the cause of glomerulonephritis and showed normal complement levels, normal coagulation profile, negative serology for viral etiology, lupus, and ANCA titers. Parathyroid hormone levels were elevated indicating a state of chronic kidney damage. ESR was elevated at 24 mm/hr but lesser than the prior admission value of 113 mm/hr and a CRP was not checked during the current admission. Urine protein to creatinine ratio was in the nephrotic range and antiglomerular basement membrane (GBM) titers were sent. Urine output recorded was between 1.5 and 2 ml/kg/hr during the initial few days but progressively got oliguric (0.3 to 0.5 ml/kg/hr) from the first week onwards. Renal ultrasound showed normal sized kidneys (right and left kidney around 7.2 cm) with increased cortical echogenicity bilaterally. A comparison of lab values during prior hospital stay and current admission is provided in Table
Comparison of lab values between prior and current admission.
Labs | 10/2015 | 5/2016 |
---|---|---|
Sodium (mmol/L) | 141 | 137 |
Potassium (mmol/L) | 4.2 | 6.0 |
Chloride (mmol/L) | 110 | 113 |
Carbon dioxide (mmol/L) | 21 | 8 |
Glucose (mg/dL) | 109 | 97 |
BUN (mg/dL) | 5 | 120 |
Creatinine (mg/dL) | 0.41 | 7.01 |
Albumin (g/dL) | 2.9 | 2.5 |
Calcium (mg/dL) | 9.3 | 5.6 |
Phosphorus (mg/dL) | 8.9 | |
White blood cell (×103/mcL) | 15.84 | 10.4 |
Hemoglobin (g/dL) | 6.9 | 7.8 |
Hematocrit (%) | 22.6 | 23.7 |
Platelets (×103/mcL) | 616 | 234 |
Ferritin (ng/mL) | 269 | 267 |
Iron (mcg/dL) | 6 | 55 |
Transferrin (mcg/dL) | 130 | 100 |
TIBC (mcg/dL) | Not done | 125 |
% saturation | Not done | 44 |
Parathyroid hormone (pg/mL) | Not done | 1031 |
C3 (mg/dL) | 166 | 114 |
C4 (mg/dL) | 30 | 48 |
ESR (mm/hr) | 113 | 12.5 |
CRP (mg/dl) | 12.5 | Not done |
Patient underwent emergent hemodialysis to correct electrolyte imbalances. We proceeded with a renal biopsy to ascertain a tissue diagnosis for the glomerulonephritis. 12 glomeruli were available for light microscopic examination. 9/12 glomeruli showed global sclerosis (Figure
Trichrome stain showing global glomerulosclerosis.
Glomerulus showing intraglomerular sclerosis.
Immunofluorescence showing linear IgG deposits.
Patient was started on high dose methylprednisolone and plasmapheresis once the biopsy results were consistent with anti-GBM disease. Anti-GBM titers (IgG antibody) also came back elevated at 1.1 units (Normal < 1) confirming the diagnosis. The subtle elevation in anti-GBM titers could be secondary to the possibility of a serological remission though chronic damage to the kidneys has already happened as documented by the amount of fibrosis on renal biopsy. Unfortunately anti-GBM titers were not checked during the initial pneumonia like presentation 7 months back which likely represented the initial acute episode. With every other day plasmapheresis, anti-GBM titers started trending down but renal function did not recover. With the extent of global sclerosis noted in renal biopsy and with the very high PTH levels, chances for renal recovery remained slim. Rituximab was used as an alternate immunosuppressive agent instead of cyclophosphamide taking into consideration the amount of chronic damage noted on renal biopsy in an attempt to reduce infectious risk. Patient received a total of 5 sessions of plasmapheresis with no improvement in renal function and was transitioned to peritoneal dialysis. During the inpatient stay she suffered a hypertensive crisis with seizures and the control of blood pressure required multiple antihypertensive agents. Anti-GBM titers were periodically monitored by lab work on a monthly basis and remained negative on maintenance immunosuppression with mycophenolate and low dose prednisone. Patient received a diseased donor kidney transplant, 2 months back, and is currently doing well with normal renal function.
GPS is a rare condition occurring in approximately 0.5 to 1 per million per year in adults and even more rare in children [
Prior reported cases of pediatric Goodpasture’s syndrome.
Age in years | Sex | Anti-GBM titers | Initial clinical presentation | Renal biopsy | Renal outcome | Pulmonary outcome | Treatment | Final outcome | Reference |
---|---|---|---|---|---|---|---|---|---|
4 | F | Positive | Pallor, fatigue oliguria, proteinuria, and microscopic hematuria with dominant renal involvement | End stage glomerulonephritis with crescent formation; linear deposition of IgG along basement membrane | No improvement | Stable | Prednisone, azathioprine, and cyclophosphamide | Died | [ |
10 | F | Positive | Gross hematuria, oliguria, and uremia with dominant renal involvement Preceding infection with strep throat | Endocapillary and extracapillary proliferative GN with 80% crescents Immunofluorescence could not be done | Dialysis dependent with no improvement | Stable | Prednisolone, azathioprine, and plasmapheresis | Remained dialysis dependent | [ |
7 | F | Positive | Diarrhea, vomiting, oliguria, and pallor with dominant renal involvement | Crescentic nephritis with linear IgG deposition | Initial improvement in urine output and GFR with subsequent decline and dialysis dependence | Stable | Plasmapheresis, prednisolone, and cyclophosphamide | Dialysis dependent | [ |
6 | M | Positive | Dominant renal involvement | Diagnostic with crescentic nephritis | Improved | Stable | Steroid, plasmapheresis, and immunosuppression | Regained renal function | [ |
10 | M | Positive | Cough, right lower lobe infiltrate, vomiting, and oliguria with dominant pulmonary involvement and pulmonary hemorrhage | Crescentic nephritis with extensive necrosis | Deterioration in renal function with dialysis dependence | Improved | Steroid, plasmapheresis, and immunosuppression | Dialysis dependent | [ |
2.5 | F | Positive | Fever, anorexia with |
Extensive crescentic necrotizing nephritis with linear IgG deposits | No improvement | Stable | Steroid, plasmapheresis, and immunosuppression | Dialysis dependent | [ |
11 months | F | Positive | Dominant renal involvement | Diagnostic with crescentic nephritis | No improvement | Stable | Steroid, plasmapheresis, and immunosuppression | Renal transplant | [ |
5.6 | F | Positive | Fever, malaise, and gross hematuria with rapid decline in renal function | Diffuse cellular crescentic nephritis with linear IgG deposits | Recovery of renal function | Stable | Plasma exchange, solumedrol, and Cytoxan | CKD with stable renal function | [ |
9 | M | Positive | Malaise, anorexia, and oligoanuria with pulmonary hemorrhage | Not done | Not improved | Pulmonary status improved | Plasma exchange, solumedrol, and Cytoxan | Dialysis dependent | [ |
8 | F | Positive | Asymptomatic with persistent nephrotic range proteinuria and microhematuria | No crescents but with linear deposits of IgG | Improvement in proteinuria with stable renal function | Stable | Plasma exchange, prednisone, and oral Cytoxan | Asymptomatic | [ |
19 months | M | Positive | Gross hematuria, proteinuria with rapid decline in renal function | Crescentic GN with weak global linear staining of IgG | Improvement in proteinuria and renal function | Stable | Plasma exchange, solumedrol, and Cytoxan | Asymptomatic | [ |
The type IV collagen which provides the backbone for GBM formation is the target for autoantibody formation and damage in GPS. The type IV collagen has six genetically discrete chains (
The specific target for autoantibody formation in GPS is the NC1 domain of the
Initial presentation of GPS can be nonspecific and often consists of symptoms such as malaise, weight loss, fever, and arthralgia [
The diagnosis of antiglomerular basement membrane disease is reliant on detection of anti-GBM antibodies either in circulation or in the tissue by means of renal or pulmonary biopsies. Serological testing for anti-GBM antibody titers (IgG1 subclass) usually employs ELISA methodology. The sensitivity of available commercial kits can vary from 63% to 100% underlying the possibility of missed diagnosis if solely reliant on serological testing [
Early diagnosis is important in terms of ability to recover renal function. Treatment of choice initially is plasmapheresis to remove circulating antibodies. The preferred immunosuppressive therapy includes corticosteroids and cyclophosphamide to reduce antibody production. Alternate immunosuppressive therapy including rituximab has been tried in resistant cases [
Unfortunately, many patients die secondary to pulmonary hemorrhage or renal failure before plasmapheresis and immunosuppression can be initiated. Currently the mortality rate is 20% in adults and 30% in children. Prognosis for renal recovery is worse in the presence of oliguria, presenting creatinine >6.8 or renal biopsy showing >50% crescent formation within glomeruli at time of diagnosis [
GPS as a cause of pulmonary renal syndrome in childhood remains extremely rare. A review of pediatric cases in the literature (Table
In conclusion, GPS is a rare autoimmune condition presenting with significant mortality and morbidity in children. We report a case of 2-year, 11-month-old child who presented with this condition and the difficulties involved in coming to an accurate diagnosis. In hindsight, her initial presentation with pneumonia was likely an occult pulmonary hemorrhage as documented by the severe anemia and iron deficiency. Her response to steroids during the initial admission likely constituted a partial treatment. GPS though rare should be considered in the differential diagnosis of clinical presentation with lung and kidney involvement and early diagnosis and intervention are essential for a favorable outcome.
The authors declare that they have no conflicts of interest.