Flares of systemic lupus erythematosus during pregnancy and the puerperium: prevention, diagnosis and management

Figures & data

Table 1. Pregnancy and fetal outcomes in systemic lupus erythematosus.

Study (year)	Pregnancies (n)	Live births (n)	Therapeutic abortions	Spontaneous abortions, n (%)	Fetal deaths, n (%)	Total pregnancy losses, n (%)	Ref.
Mintz et al. (1987)	102	80 (78%)	0	17 (17%)	5	22 (22%)	[28]
Huong et al. (1997)	62	51 (77%)	2 (3%)	10 (16%)	2 (3%)	12 (19%)	[105]
Lima et al. (1995)	108	89 (82%)	2 (2%)	7 (7%)	10 (9%)	19 (18%)	[106]
Georgiu et al. (2000)	59	36 (61%)	3 (5%)	9 (15%)	1 (2%)	13 (22%)	[107]
Cortes-Hernandez et al. (2002)	103	68 (66%)	8 (8%)	15 (15%)	12 (12%)	35 (34%)	[12]
Liu et al. (2012)	111	83 (75%)	23 (20%)	2 (2%)	8 (9%)	10 (11%)	[108]
Gladman et al. (2011)	193	114 (59%)	31 (16%)	42 (21%)	3 (2%)	79 (41%)	[109]
Al Arfaj et al. (2010)	383	269 (70.2%)	NA	94 (25%)	20 (5%)	114 (30%)	[110]
Ko et al. (2011)	183	152 (83%)	NA	17 (9%)	12 (7%)	29 (16%)	[111]
Clowse et al. (2006)	267	229 (86%)	NA	19 (7%)	19 (7%)	27 (14%)	[38]

NA: Not available.

Table 2. Flare rates in systemic lupus erythematosus.

Study (year)	Pregnancies (n)	Controls	Flare definition	Pregnancy flares (%)	Ref.
Flare rate similar in and out of pregnancy
Lockshin et al. (1984)	33	Matched, nonpregnant	Custom	27	[33]
Mintz et al. (1986)	92	Matched, nonpregnant	Custom	59	[28]
Urowitz et al. (1993)	79	Matched, nonpregnant with and without active SLE	Custom	70	[34]
Tandon et al. (2004)	78	Matched, nonpregnant	Renal activity	45	[35]
Increased flare rate in pregnancy
Petri et al. (1991)	40	Matched, nonpregnant	PGA	60	[29]
Wong et al. (1991)	29	Nonpregnant	Custom, modified from Lockshin	58	[33,36]
Ruiz-Irastroza et al. (1996)	78	Matched, nonpregnant and postpregnancy course	LAI	65	[37]

LAI: Lupus activity index; PGA: Physician global assessment; SLE: Systemic lupus erythematosus.

Table 3. Assessment of lupus flares in pregnancy.

Feature	Findings indicative of a lupus flare	Findings of normal pregnancy that can mimic a flare
Clinical	Active rash of lupus Inflammatory arthritis Lymphadenopathy	Fatigue Arthralgias Bland effusions of knees
	Fever >38°C (not related to infection or drug)	Myalgias Malar and palmar erythema Postpartum hair loss
	Pleuritis	Carpal tunnel syndrome Edema of hands, legs, and face Mild resting dyspnea
	Pericarditis
ESR	Increased	18–46 mm/h <20 weeks gestation 30–70 mm/h ≥20 weeks gestation [112]
Anemia	Hemoglobin <10.5 g/dl	Hemoglobin >11 g/dl during first 20 weeks gestation Hemoglobin >10.5 g/dl after 20 weeks gestation [113]
Thrombocytopenia	Platelet count <95,000/μl	Mild in approximately 8% [55]
Urinalysis	Hematuria or cellular casts	Rare hematuria from vaginal contamination
Proteinuria	≥300 mg/day	<300 mg/dl
dsDNA antibodies	Rising titers	Negative or stable titers
Complement	≥25% drop	Usually increased

ESR: Erythrocyte sedimentation rate. Reproduced with permission from [114].

Table 4. Lupus Activity Index in Pregnancy.

Group	Parameter	Point values				Values to calculate LAI-P
1	Fever	0	1			(a) Mean
	Rash	0		2
	Arthritis	0		2	3
	Serositis	0	1	2	3
2	Neurologic	0			3	(b) Maximum
	Renal	0		2	3
	Lung	0			3
	Hematologic	0	1	2	3
	Vasculitis	0			3
	Myositis	0			3
3	Prednisone, NSAID, HCQ	0	1	2	3	(c) Mean
	Immunosuppressor	0			3
4	Proteinuria	0	1	2	3	(d) Mean
	Anti-DNA	0	1	2
	C3, C4	0	1	2

Point value of LAI-P = (a + b + c + d)/4.

HCQ: Hydroxychloroquine; LAI-P: Lupus Activity Index in Pregnancy.

Table 5. Modification of SELENA–SLEDAI for assessment of systemic lupus erythematosus disease activity in pregnancy.

SELENA–SLEDAI			SLEPDAI	Comment
Descriptor	Score		Modified for pregnancy
Seizure	8		Yes	r/o eclampsia
Psychosis	8		No
Organic brain syndrome	8		No
Visual disturbance	8		Yes	Hypertension
Cranial nerve disorder	8		Yes	r/o Bell’s palsy
Lupus headache	8		Yes	r/o eclampsia, preeclampsia
CVA	8		Yes	r/o eclampsia
Vasculitis	8		Yes	Consider palmar erythema
Arthritis	4		Yes	Consider bland knee effusions
Myositis	4		No
Urinary casts	4		No
Hematuria	4		Yes	r/o cystitis and vaginal bleeding reflective of placental problems
Proteinuria	4		Yes	r/o eclampsia
Pyuria	4		Yes	r/o infection
Rash	2		Yes	Consider chloasma
Alopecia	2		Yes	Consider normal postpartum alopecia
Mucosal ulcers	2		No
Pleurisy	2		Yes	Hyperventilation secondary to progesterone, dyspnea secondary to enlarging uterus
Pericarditis	2		No
Low complement	2		Yes	Complements normally rise during pregnancy
Increased DNA binding	2		No
Fever	1		No
Thrombocytopenia	1		Yes	r/o preeclampsia, HELLP, incidental thrombocytopenia of pregnancy
Leukopenia	1		Yes	Consider normal rise of leukocyte count during pregnancy

Total score (sum of weights next to descriptors marked present).

CVA: Cerebrovascular accident; HELLP: Hemolysis elevated liver enzymes low platelet count; r/o: Rule out; SELENA: Safety of Estrogens in Lupus Erythematosus National Assessment; SLE: Systemic lupus erythematosus; SLEDAI: SLE Disease Activity Index.

Reproduced with permission from [57].

Table 6. Differentiation of active lupus nephritis from preeclampsia.

Clinical and laboratory features	Active lupus nephritis	Preeclampsia
Hypertension	Onset before 20 weeks	Onset after 20 weeks
Proteinuria	≥300 mg/day	≥300 mg/dl
Urinary sediment	Active	Inactive
Uric acid	≤5.5 mg/dl	>5.5 mg/dl
DNA antibody levels	Rising	Stable or negative
24 h urine calcium	≥195 mg/day	<195 mg/day
Complement levels	≥25% drop	Normal

Reproduced with permission from [114].

Table 7. Differentiation of microangiopathies in lupus pregnancy.

Features	HELLP	AFLP	TTP	CAPS
Fever	-	++	+++	+
Jaundice	+	+++++	+	+
Lung involvement	-	-	-	++++
Elevated liver enzymes	+++++	+++++	+++	+
Impaired renal function	+++	+++++	++	++++
Elevated bilirubin	+++	+++++	+++++	+
Hepatic infarcts	+	-	-	+
Hypertension	++++	++	+++	+
DIC	+++	++++	-	+
Microangiopathic hemolytic anemia	+++++	+	+++++	+
Thrombocytopenia	+++	-	+	+++
Hypoglycemia	-	+++	-	-
ADAMTS13 <5%	-	-	+++++	-

+: 0–20% approximate frequency; ++: 20–40%; +++: 40–60%; ++++: 60–80%; +++++: 80–100%; -: Does not occur; ADAMTS: A disintegrin and metalloproteinase with thrombospondin type-1 motifs; AFLP: Acute fatty liver of pregnancy; CAPS: Catastrophic antiphospholipid antibody syndrome; DIC: Disseminated intravascular coagulation; HELLP: Hemolysis, elevated liver enzymes and low platelets; TTP: Thrombotic thrombocytopenic purpura.

Adapted from [84,103,115,116].

Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

Mintz G, Niz J, Gutierrez G, Garcia-Alonso A, Karchmer S. Prospective study of pregnancy in systemic lupus erythematosus. Results of a multidisciplinary approach. J. Rheumatol. 13(4), 732–739 (1986).

 PubMed Web of Science ®Google Scholar

Lê Huong D, Wechsler B, Vauthier-Brouzes D et al. Outcome of planned pregnancies in systemic lupus erythematosus: a prospective study on 62 pregnancies. Br. J. Rheumatol. 36(7), 772–777 (1997).

 PubMedGoogle Scholar

Lima F, Buchanan NM, Khamashta MA, Kerslake S, Hughes GR. Obstetric outcome in systemic lupus erythematosus. Semin. Arthritis Rheum. 25(3), 184–192 (1995).

 PubMed Web of Science ®Google Scholar

Georgiou PE, Politi EN, Katsimbri P, Sakka V, Drosos AA. Outcome of lupus pregnancy: a controlled study. Rheumatology (Oxford) 39(9), 1014–1019 (2000).

 PubMed Web of Science ®Google Scholar

Cortés-Hernández J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M. Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies. Rheumatology (Oxford) 41(6), 643–650 (2002).

 PubMed Web of Science ®Google Scholar

Liu J, Zhao Y, Song Y et al. Pregnancy in women with systemic lupus erythematosus: a retrospective study of 111 pregnancies in Chinese women. J. Matern. Fetal. Neonatal. Med. 25(3), 261–266 (2012).

 PubMed Web of Science ®Google Scholar

Gladman DD, Tandon A, Ibañez D, Urowitz MB. The effect of lupus nephritis on pregnancy outcome and fetal and maternal complications. J. Rheumatol. 37(4), 754–758 (2010).

 PubMed Web of Science ®Google Scholar

Al Arfaj AS, Khalil N. Pregnancy outcome in 396 pregnancies in patients with SLE in Saudi Arabia. Lupus 19(14), 1665–1673 (2010).

 PubMed Web of Science ®Google Scholar

Ko HS, Ahn HY, Jang DG et al. Pregnancy outcomes and appropriate timing of pregnancy in 183 pregnancies in Korean patients with SLE. Int. J. Med. Sci. 8(7), 577–583 (2011).

 PubMed Web of Science ®Google Scholar

Clowse ME, Magder LS, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum. 52(2), 514–521 (2005).

 PubMed Web of Science ®Google Scholar

Lockshin MD, Reinitz E, Druzin ML, Murrman M, Estes D. Lupus pregnancy. Case–control prospective study demonstrating absence of lupus exacerbation during or after pregnancy. Am. J. Med. 77(5), 893–898 (1984).

 PubMed Web of Science ®Google Scholar

Urowitz MB, Gladman DD, Farewell VT, Stewart J, McDonald J. Lupus and pregnancy studies. Arthritis Rheum. 36(10), 1392–1397 (1993).

 PubMed Web of Science ®Google Scholar

Tandon A, Ibañez D, Gladman DD, Urowitz MB. The effect of pregnancy on lupus nephritis. Arthritis Rheum. 50(12), 3941–3946 (2004).

 PubMed Web of Science ®Google Scholar

Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis Rheum. 34(12), 1538–1545 (1991).

 PubMed Web of Science ®Google Scholar

Ruiz-Irastorza G, Lima F, Alves J et al. Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br. J. Rheumatol. 35(2), 133–138 (1996).

 PubMedGoogle Scholar

van den Broe NR, Letsky EA. Pregnancy and the erythrocyte sedimentation rate. BJOG 108(11), 1164–1167 (2001).

 PubMed Web of Science ®Google Scholar

Maternal Health and Safe Motherhood Programme. Prevention and Management of Severe Anaemia in Pregnancy: Report of a Technical Working Group, Geneva, 20–22 May 1991. WHO, Division of Family Health, Geneva, Switzerland (1993).

 Google Scholar

Burrows RF, Kelton JG. Incidentally detected thrombocytopenia in healthy mothers and their infants. N. Engl. J. Med. 319(3), 142–145 (1988).

 PubMed Web of Science ®Google Scholar

Baer AN, Witter FR, Petri M. Lupus and pregnancy. Obstet Gynecol Surv. 66(10), 639–653 (2011).

 PubMed Web of Science ®Google Scholar

Buyon JP, Kalunian KC, Ramsey-Goldman R et al. Assessing disease activity in SLE patients during pregnancy. Lupus 8(8), 677–684 (1999).

 PubMed Web of Science ®Google Scholar