A Pregnant Women With Dyspnea and seizure: First Manifestations Of Granulomatosis with polyangiitis:

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A Pregnant Women With Dyspnea and seizure: First Manifestations Of  Granulomatosis with polyangiitis:

Masoumi M1*2, Kamelian Z1, Haghighi A1, Shajari R1, Sharifipoor E1, Asghari A1

  1. 1Qom University of Medical Science. Qom. Iran
  2.  

    2Rheumatology Research Center, TUMS. Tehran. Iran

    *Corresponding author: Dr. Masoumi M, Qom University of Medical Science, Shahid Beheshti Hospital, Internal Medicine Department. Qom. Iran. Tel: +98 919 012 3098; Email: m.masoumiy@gmail.com

Abstract

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which has a variable clinical presentation and usually progresses from a localized to a generalized form over the course of weeks to years. Histopathologically, it is a necrotizing systematic vasculitis that can cause sino-nasal, pulmonary, renal, ocular, and cutaneous manifestations. Diagnostic workup should include serologic, radiologic, endoscopic and histopathological examination. Autoantibody c-ANCA may be used as a marker of disease activity and individual follow-up. An appropriate local and systemic treatment should be implemented, which is particularly important in pregnancy. Comprehensive management should be planned, including the needs of both mother and fetus (particularly if vasculitis is diagnosed de novo during pregnancy). Pregnancy in patients with GPA is burdened with the risk of possible complications and increased mortality and the conception should be delayed until remission of the disease. A flare-up of GPA may be life threatening for both mother and fetus. The presence of inflammatory granulomatous lesions in the respiratory system should be proved to make a diagnosis of GPA, but clinical manifestations and laboratory findings are frequently used instead. The etiology of GPA is still unknown but there are evidences based on an autoimmune disorder, and ANCA that plays an important role in this disease . The pregnancy outcome in patients with AAV(Antineutrophil cytoplasmic antibody–associated vasculitis) in remission was excellent. Pregnancy in women with AAV in remission does not seem to be associated with increased risk of relapse In this article, we present a case of GPA who had her first presentation during pregnancy.

Keywords

Granulomatosis with polyangiitis;  Pregnancy;  Treatment

Case Report

The patient 36 years old was a pregnant woman, G1P1Ab0, 17 w gestational age, who was visited at the emergency department complaining of productive cough, fever, severe weakness and lethargy, and dyspnea. Antibiotic therapy with ceftriaxone was started. During hospitalization, the patient’s dyspnea became worse and O2 saturation fell and she had recurrent and refractory seizures. Meanwhile, PTE was suspected. Intubation was performed, that for MRI and other diagnostic procedures couldn’t be done. CXR was requested for the patient because antibiotic therapy was unsuccessful and O2 saturation was falling. CXR findings included cavity and granulomatous lesions. With a high ESR in laboratory findings and granulomatous lesions on CXR and a history of sinusitis, GPA was suspected. Meanwhile, the patient developed hemoptysis and renal involvement with gross hematuria, without dysmorphic RBC, and proteinuria more than 500 mg /24h, disrupted liver function test( LFT), and decreased platelet count, and brain involvement with seizure that was resistance to therapy, suggesting a multisystem disease. Based on the clinical manifestations and laboratory findings, GPA was a likely diagnosis for the patient. The patient was scheduled for bronchoscopy twice but she couldn’t tolerate it because of falling in O2 saturation and increased hypoxia. Even though the diagnosis of GPA requires the proof of inflammatory geranulomatous lesions, it is basically based on clinical and paraclinical findings. c- antineutrophil cytoplasmic antibodies (c-ANCA) was positive 3 times. A c-ANCA level above 200 was reported and HRCT was performed to confirm the diagnosis pattern of alveolar hemorrhage and multiple nodules was seen. The patient received 3 pulses of methylprednisolone intravenously followed by prednisolone 1mg/kg, and, Intra venous Immunoglobulin (IVIG) for 5 days with plasmapheresis for 7 days, levebel 3000 mg at first then continued 1000mg daily, and prophylaxis of cotrimoxazole every other day and pulse cyclophosphamide 1gr in the first followed by 500 mg every 2 weeks for 1 month and then 500 mg/m along with monitoring of the fetal condition. The patient responded well to treatment but had a preterm labor (32W + 3D). A healthy female IUGR infant weighing 2.5 kg was born and treatment continued. Patient performed MRI after the life threatening state was passed, and referred to neurologist which had no specific problem. Patient’s general status while hospitalization was so poor that we chose to start cyclophosphamide, but we didn’t find any necessity to perform kidney biopsy. Because the diagnosis was done and patient responded dramatically to cyclophosphamide and prednizolone, which indicates that we are dealing with a GPA and not a malignancy or infection.

 

Lab test:

First count blood cell( CBC){WBC:12800  , Hemoglobin:10.2  ,Platelet:399000-34000}

Final CBC{Wbc:2400  , Hemoglobin:8.4  , Platelet:191000}

 

First Creatinin:0.8  ,  0.7 ,  1     Final:0.7

 

First LFT{ALT:227(>32)    ,AST:58(>38)    ,Alkph:303}

Final LFT{ ALT:213,     AST:173,      AKP:236}

 

ESR:152 ,132     CRP:77,87(>15)

 

Urine(Urine 24h/cr:900  Urine 24h/Pr:765    Urine 24h/Volume:2500)

 

Urine/Analysis{Protein:Trace   Blood:+++    RBC:Many }

 

 

CANCA(anti PR-3): >200      PANCA(Anti MPO): Negative     fluoerscent antinuclear antibody(FANA): Negative

Anti dsDNA:  Negative

Anti-glomerular basement membrane==Negative    C3=NL     C4=NL    CH50=NL

HCV Ab= Negative     HIV Ab= Negative     HBs Ag= Negative

 

Discussion

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which has a variable clinical presentation and usually progresses from a localized to a generalized form over the course of weeks to years[1].  There are only few reports of GPA in pregnancy and no information is available about the relationship between GPA and pregnancy. However, there are reports of six GPA cases in pregnancy, of whom 3 ended in premature delivery [2 – 4], 2 ended in abortion[5,6], and 1 ended in maternal death[7]. In all six cases, the disease recurred 2 – 8 weeks after delivery[8,9]. In another study the pregnancy outcome in patients with AAV(Antineutrophil cytoplasmic antibody–associated vasculitis) in remission was excellent. Pregnancy in women with AAV in remission does not seem to be associated with increased risk of relapse[10 -12].  In our case, the disease occurred during pregnancy, and pregnancy played an important role in its flare, but its relationship is not quietly undrestanded yet. Disease activity is usually seen in the first and second trimester. Although the first occurrence of GPA in pregnancy and disease activity in this period is a prognostic factor for its duration and pregnancy outcome[13,14], this disease has a poor outcome. Prematurity is a common complication in pregnant patients. The mean gestational age at delivery is 36 weeks[15-17]. The most specific laboratory data for diagnosis of GPA is cANCA by IIF(Indirect immunofluorescence)[18]. Corticosteroids are a known risk factor for preterm delivery. The treatment of GPA is a challenge and prednisolone and cyclophosphamide are used to control the disease during pregnancy. Progression of the disease is reported in patients who only receive prednisolone. The choice of treatment depends on the severity of the disease and the stage of pregnancy. The most common medication in pregnancy is prednisolone[19]. The choice of treatment depends on the severity of the disease and the stage of pregnancy. The most common medication in pregnancy is prednisolone. In pregnant women with mild GPA, prednisolone alone is the treatment of choice while cyclophosphamide and prednisolone are used for moderate to severe cases in the second and third trimester[20]. however patients with systemic vasculitis can have successful pregnancies[21].

Our cases was first presentation of severe disease with involvement in lung and lower respiratory and kidney that manifestations was started in pregnancy. She was responded excellent with prednisolone and cyclophosphamide with good outcome her child.

Conclusion

There is limited information about the management of GPA in pregnancy. In the reported this case report, because the disease was diagnosed after 20 weeks’ gestation, abortion was not indicated and the patient responded well to the treatment; the mother and the fetus were both well protected and the disease subsided. The baby was born at 32W + 3D. The mother suffered from premature rupture of membrane (PROM), which was most probably a consequence of the drugs used for the treatment of GPA.

References

 

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