- Case report
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Systemic vasculitis diagnosed during the post-partum period: case report and review of the literature
Maternal Health, Neonatology and Perinatology volume 9, Article number: 2 (2023)
The vasculitis diagnosed specifically in the post-partum period are less well known. We report here such a case followed by a descriptive review of the literature.
A 25 year-old French nurse reported abrupt-onset musculoskeletal pain 15 days after delivery of her first infant. Her first pregnancy was uneventful. The physical examination yielded only bilateral conjunctivitis and purpuric eruption of lower limbs, and complementary investigations evidenced pulmonary renal syndrome in connection with the diagnosis of Granulomatosis with Polyangiitis.
We screened previous articles in Medline database using keywords (i) “post-partum” or “puerperium” (ii)”peripartum” (iii) “pregnancy” associated with “vasculitis”. Full texts were obtained from case reports or cases series whose title or abstract included keywords of interest (or synonyms). These references were secondarily excluded if the diagnosis of vasculitis was not confirmed or made before or more than 6 months after delivery and if vasculitis occurred only in the new born or affected only the cerebral vasculature or the retina.
Fifty-six cases of vasculitis diagnosed in the post-partum period were included, 50 (89.3%) were secondary to an immunological process and 44 corresponded to primary vasculitis, 4 were secondary to Systemic Lupus Erythematosus, 1 to cryoglobulinaemia and 1 to cryoglobulinaemia associated with inflammatory bowel disease. The main primary vasculitis diagnosed were Takayasu Arteritis (n = 10), Eosinophilic granulomatosis with polyangiitis (n = 9), Granulomatosis with Polyangiitis (n = 7), Periarteritis Nodosa (n = 5) and Behcet’s disease (n = 4). The first symptom occurred before delivery in 26 (59.1%) and maternal death occurred in 4 (9.1%) out of the 44 primary vasculitis cases.
The vasculitis diagnosed in the post-partum period were mainly primary vasculitis among patients in whom the diagnosis had not been made during pregnancy. In less than half of cases and as described in ours, there were no reported symptoms before delivery. Therefore, the physicians should pay attention to symptoms and keep a high degree of suspicion for vasculitis before as well as after delivery.
Systemic vasculitis represent a wide range of diseases that can be either primary as well as secondary to other processes such as drug exposure, connective tissue disease or infection . Despite several changes during the last years , the nomenclature of non-infectious vasculitis is now based on the Chapel Hill classification .
While previously discouraged, pregnancy is now described among women suffering from non-infectious systemic vasculitis . The outcome of such pregnancies is reported to be worst when vasculitis was active before pregnancy or diagnosed during pregnancy [3, 4].
However, there are less data concerning systemic vasculitis diagnosed specifically in the post-partum period. We describe here a case of primary systemic vasculitis diagnosed in the post-partum period, without any symptoms during pregnancy, before we make a descriptive review of the literature focusing on vasculitis diagnosed specifically in the post-partum period.
A 25 year-old French nurse reported abrupt-onset musculoskeletal pain 15 days after delivery of her first infant. She had no past medical history and did not report any tobacco smoking, intravenous drug use or trip abroad. Her first pregnancy was uneventful except gestational diabetes. She gave birth to a healthy female neonate after an uncomplicated vaginal delivery. Fifteen days later, she reported diffuse joint pain without swelling. The pain was maximum in the morning and the joints affected were knees, ankles, wrists and shoulders. Bilateral conjunctivitis then purpuric eruption of lower limbs occurred one month after delivery. Despite a 14-day course of amoxicilline plus clavulanate (without any effect on symptoms), she was admitted to hospital because of hypochromic microcytic anaemia (7.3 g/dL; 11.5 < N < 15.1 g/dL) associated with thrombocytosis (491 000/mm3; 150 000 < N < 400 000/mm3) and elevated Serum C reactive protein (180 mg/L; N < 5 mg/L) and ferritin (560 ng/mL; 13 < N < 150 ng/mL) values. Physical examination evidenced only aphthae and small petechiae on the inner part of the leg, but no joint effusion or fever. Blood Creatinine level and proteinuria were 96 µmol/L (45 < N < 80 µmol/L) and 3000 mg/day (N < 150 mg/day) respectively. Chest X-Ray and Ct chest Scan yielded bilateral cavitary lung lesions (Fig. 1). Sputum Acid Fast Bacillus smears were negative as well as QuantiFERON®-TB Gold and blood cultures. Transthoracic Echocardiography was normal. Serum Anti -proteinase 3 antibodies level was 110UI/mL (N < 2UI/mL) and the diagnosis of Granulomatosis with Polyangiitis was retained. Outcome was favourable once methylprednisolone intravenous bolus (1000 mg/day for three days then oral prednisone 1 mg/kg/day during three weeks before progressive tapering (5 mg decrease weekly up to 30 mg, then 5 mg decrease every 2 weeks up to 15 mg, then 12 mg/day during 2 weeks, then 10 mg/day during 2 weeks before final 1 mg decrease every 2 weeks up to 5 mg/day)) and rituximab (375 mg/m2 weekly during four weeks followed by maintenance therapy with 500 mg every six months) were prescribed to the patient, who gave her written consent to report her case.
We made a literature review (i) to define which kinds of vasculitis were diagnosed specifically in the post-partum period (ii) to estimate how many cases of vasculitis did not have any symptoms before delivery (iii) to describe the outcome of vasculitis diagnosed in the post-partum period.
We conducted a review of cases of vasculitis whose diagnosis was made in the post-partum period. We first screened previously published articles in Medline database using keywords “post-partum” or “puerperium” associated with “vasculitis” or “vasculitides” without time limits. Articles whose title or abstract included keywords of interest “post-partum” and/or “vasculitis” (or synonyms or causal conditions) were selected (YNG). Full text versions were obtained and only case reports or cases series with available clinical data were included; review without case reports, epidemiological works without clinical data and animal data were not included. These references were secondarily excluded (i) in case of duplicate references (ii) if the diagnosis of vasculitis was not confirmed (iii) if the diagnosis of vasculitis was made before or more than 6 months after successful delivery of a living new-born (excluding miscarriage) (iv) if vasculitis occurred only in the new born but not in the mother (v) if vasculitis related to an immunological process only affected the cerebral vasculature or the retina.
A second search in Medline using keywords “peripartum” associated with “vasculitis” or “vasculitides” without time limits was then conducted. A third search in Medline using keywords “pregnancy” associated with “vasculitis” or “vasculitides” without time limits but restricted to case reports was also conducted. A last search was conducted by checking references of previously selected references. In all these cases, the same methodology stated above to include and exclude references was applied (YNG).
The flow chart of selected references is depicted in Fig. 2. All co-authors extracted from each case described in these references, the diagnosis of vasculitis, the symptoms and their onset as well as the pregnancy complications and the outcome. Each case was categorized in vasculitis secondary to an infectious process, vasculitis secondary to a drug exposure and vasculitis related to an immunological process (primary or secondary to connective tissue diseases, cryoglobulinemia…). The results were expressed as tables for clarity purpose and a qualitative descriptive synthesis was ultimately performed.
Fifty-six cases out of 56 references were included (Fig. 2). Among these 56 cases of vasculitis diagnosed in the post-partum period, 4 (7.1%) corresponded to vasculitis secondary to an infectious origin (Table 1) [5,6,7,8] and 2 (3.6%) corresponded to vasculitis secondary to a drug exposure (Table 2) [9, 10]. Fifty out of the 56 cases (89.3%) corresponded to vasculitis secondary to an immunological process (Table 3) [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60]. Among these 50 cases, 44 (88.0%) corresponded to primary vasculitis, 4 were secondary to Systemic Lupus Erythematosus [26, 41, 50, 60], 1 to cryoglobulinaemia  and 1 to cryoglobulinaemia associated with inflammatory bowel disease .
The primary vasculitis diagnosed were Takayasu Arteritis (n = 10) [17, 19, 36, 39, 40, 43, 49, 52, 54, 59], Eosinophilic granulomatosis with polyangiitis (n = 9) [20, 21, 24, 42, 44, 46, 55,56,57], Granulomatosis with Polyangiitis (n = 7) [13, 25, 32, 45, 47, 51, 53], Periarteritis Nodosa (n = 5) [16, 27, 29, 37, 58], Behcet’s disease (n = 4) [12, 23, 35, 38], Henoch-Schönlein purpura (n = 3) [15, 28, 31], Microscopic polyangiitis and Kawasaki Disease (two cases each) [11, 18] and [22, 30], Buerger’s disease and Cutaneous leukocytoclastic angiitis (one case each)  and .
Among the 44 primary vasculitis diagnosed in the post-partum period, the first symptom occurred before delivery in 26 cases (59.1%) [11, 15, 17,18,19,20, 27, 30, 32,33,34,35, 38,39,40, 42, 43, 45, 47, 48, 52, 54, 56,57,58, 60]. Among the 6 vasculitis secondary to Systemic Lupus Erythematosus and cryoglobulinaemia [14, 26, 34, 41, 50, 60], the first symptom of vasculitis occurred before delivery in 2 cases only (33.3%) [34, 60]. There was no pregnancy complications in 11 out of the 28 (39.2%) vasculitis cases secondary to an immunological process (primary and secondary) whose first symptom occurred before delivery and in 11 out of 22 (50.0%) vasculitis cases secondary to an immunological process (primary and secondary) whose first symptom occurred after delivery. Maternal death occurred in 4 out of the 44 primary vasculitis (9.1%) [13, 27, 56, 58] and in 4 out of the 6 vasculitis (66.6%) secondary to Systemic Lupus Erythematosus and cryoglobulinaemia [14, 26, 41, 60]. Two infants born to mothers with vasculitis symptoms before delivery experienced vasculitis a few days after birth [33, 38].
In this review, the systemic vasculitis diagnosed in the post-partum period (i.e. during the first 6 months following delivery) were mainly due to an immunological process and corresponded to primary vasculitis in more than 75% of cases. All kinds of vasculitis have been described (large, medium and small vessels) but the five most common diagnoses were Takayasu Arteritis, Eosinophilic granulomatosis with polyangiitis, Granulomatosis with Polyangiitis, Periarteritis Nodosa and Behcet’s Disease. In less than half of cases, there were no symptoms reported before delivery, but in the other half, reported symptoms did not lead to a diagnosis before delivery and to the exclusion from this review (see exclusion criteria above). The maternal mortality of the primary vasculitis diagnosed in the post-partum period was less than 10%, but the maternal mortality of the vasculitis secondary to Systemic Lupus Erythematosus and cryoglobulinaemia appeared higher, within limitations of a low number of cases.
Among primary vasculitis (which accounted for the majority of vasculitis diagnosed in the post-partum period), the distribution of the diagnosis was close to that observed during pregnancy , suggesting that vasculitis diagnosed in the post-partum were the continuity of those diagnosed during pregnancy and therefore belonged to the same nosological entity. Indeed, most authors of such cases considered post-partum as a part of pregnancy because more cases were retrieved with the keyword “pregnancy” than with the keyword “post-partum” or “puerperium” (Fig. 2).
The most frequently described vasculitis in our review and in that of Gatto and colleagues focusing on pregnancy  was Takayasu Arteritis. It was the sole vasculitis involving large arteries described because, unlike giant cell arteritis, it occurred especially among women of childbearing age. Moreover, Takayasu Arteritis is likely to be overrepresented in this review focusing on vasculitis diagnosed within 6 months post-delivery, because angiographic investigations required to confirm the diagnosis were performed after delivery in all cases [17, 19, 36, 39, 40, 43, 49, 52, 54, 59]. The risk of intra-uterine growth restriction, the need of close monitoring of Blood Pressure and the anaesthetic management of Takayasu Arteritis during labour have been reviewed elsewhere [3, 61,62,63,64].
Periarteritis nodosa was the main vasculitis involving medium arteries in our review and in that of Gatto . The main vasculitis involving small arteries were Eosinophilic granulomatosis with polyangiitis and Granulomatosis with Polyangiitis, 2nd and 3rd most common vasculitis in our review versus 4th and 3rd in the review of Gatto and colleagues . Why Behcet’s disease (vasculitis involving variable vessels including veins ) was underrepresented in our review (5th more common diagnosis versus 2nd in the review of Gatto and colleagues ) remained misunderstood. Maybe it could be due to a reporting bias and to undiagnosed Behcet’s diseases in the post-partum when considering genital ulcerations or deep vein thrombosis as genuine complications of delivery.
Within limitations of a low number of cases, the vasculitis secondary to Systemic Lupus Erythematosus and cryoglobulinaemia seemed to have a higher occurrence of symptoms after delivery and a higher mortality than primary vasculitis. In those latter, the diagnosis was not made before delivery even if the first symptoms occurred before delivery in 59.1% of cases. The occurrence of neonatal vasculitis was only observed in two infants born to mothers with vasculitis symptoms before delivery [33, 38]. All these assertions suggested that the physicians should pay attention to symptoms and keep a high degree of suspicion for vasculitis before as well as after delivery. We agreed that we should remain cautious when analysing mortality from these cases included during a large time period with different practices for diagnosis as well as for therapeutic purposes.
The main limitation of this review remains its non-exhaustive nature. Even if we try to build a systematic reproducible review, some relevant references were found out of the scope of the search we made . Conversely, we were unable to find some full texts [66, 67]. Moreover, we exclude references with unconfirmed diagnosis , very uncertain timelines  or diagnosis made more than 6 months after delivery , because 6 months is considered as the maximal length of the post-partum period for some authors  and as the time delay during which the hormonal environment leading to ovulation has not been restored in more than 80% of breastfeeding women of Western countries . The cases of vasculitis affecting only the neonate  were out of the scope of this review, as well as the cases of vasculitis related to an immunological process involving only the cerebral vasculature or the retina [74, 75]. In these cases, other pathological processes such as vasospasm could not be ruled out as a differential diagnosis of vasculitis [76,77,78]. Although non-exhaustive, we tried to make this review as systematic as possible.
In conclusion, the data from this review suggested that the vasculitis diagnosed in the post-partum period were mainly primary vasculitis among patients in whom the diagnosis has not been made during pregnancy. In less than half of cases and as described in ours, there were no reported symptoms before delivery. Therefore, the physicians should pay attention to symptoms and keep a high degree of suspicion for vasculitis before as well as after delivery.
Availability of data and materials
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
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the authors are indebted to Amelie Servettaz and Ailsa Robbins for their help while preparing this manuscript.
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Demotier, S., Orquevaux, P. & N’Guyen, Y. Systemic vasculitis diagnosed during the post-partum period: case report and review of the literature. matern health, neonatol and perinatol 9, 2 (2023). https://doi.org/10.1186/s40748-023-00147-3