Headache and Systemic Lupus Erythematosus

Abstract and Introduction

Abstract

Objective: To review the epidemiology, the differential diagnosis, and the clinical and laboratory factors associated with the care management of headaches in patients with systemic lupus erythematosus (SLE).

Background: SLE is a chronic autoimmune disease and in 12%–95% of patients, the nervous system is involved. Headache is a frequently reported, although nonspecific, symptom that may potentially represent serious underlying diagnoses. Primary headaches may also occur in these patients, thereby causing a negative and significant impact on their quality of life.

Methods: This is a narrative review. A literature review was conducted on the PubMed platform using the following terms: (1) headache and (2) lupus. All articles considered relevant were included. No limitations were imposed for the publication date.

Results: Headache is a frequent symptom in patients with SLE. Although its prevalence is similar to the general population, headaches nonetheless tend to have a greater negative impact on these patients. Patients with SLE are more likely to experience headache due to vascular diseases such as cerebral venous sinus thrombosis, stroke, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome, and vasculitis. Aseptic meningitis, neuroinfections, intracranial neoplasms, and intracranial hypertension or hypotension may also be a cause of headache in these patients. Although used in disease activity scores, the concept of lupus headache is controversial.

Conclusions: Headache is a frequent symptom in patients with SLE. An appropriate approach enables the potentially serious conditions, which are the causes of secondary headaches, to be recognized and treated, together with an appropriate diagnosis and treatment of primary headaches.

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune and potentially fatal disease. It affects predominantly women between puberty and menopause with a disproportional female/male ratio of approximately 9:1.^[1] Its prevalence varies considerably across different regions of the world, ranging from 48 to 367 per 100,000 inhabitants in the United States.^[2] A recent meta-analysis estimated a prevalence of 72.8 per 100,000 person-years in the United States.^[3]

The pathophysiology of SLE is complex and involves the dysregulation of the innate and adaptive immune systems, resulting in an inappropriate autoimmune response against particles containing nucleic acids.^[1] The loss of self-tolerance leads to the generation of autoantibodies, immune complexes, and autoreactive T cells, and the production of inflammatory cytokines, resulting in multisystemic involvement.^[4]

The involvement of the nervous system occurs in 12%–95% of patients with SLE. This variation may be explained by methodological differences between the studies, including the design (prospective or retrospective), the characteristics of the population assessed, and the different ways to attribute neurological symptoms to SLE.^[5]

Headache is a frequently reported symptom in patients with SLE and may represent potentially dangerous underlying diagnoses;^[6] however, primary headaches may also occur in patients with SLE. These have a negative, significant impact on quality of life and require an appropriate diagnosis and treatment.^[7]

The aim of this article is to review the epidemiology, the differential diagnosis, the associated clinical and laboratory factors, and the treatment of headache in patients with SLE.

Table 1. Summary of controlled studies relating headaches and systemic lupus erythematosus.
Primary author/Year	Sample	Data collection	ICHD	Headache definition	Headache and SLE^a	Migraine and SLE	TTH and SLE
Whitelaw, 2004²⁷	SLE (N = 85) Emergency nurses (N = 61)	Face-to-face interview with questionnaire	Yes (ICHD 1)	ICHD criteria and questionnaire used	61% × 89%	NR	NR
Appenzeller, 2004²⁸	SLE (N = 85) Control group 1: patients with RA (N = 40) Control group 2: patients with no autoimmune disease (N = 40)	Face-to-face interview with questionnaire	Yes (ICHD 1)	Patients with a history of migraine (before the rheumatological disease); a family history of migraine; acute, mild, and non-recurrent headache were excluded	NR	42.5% × 12.5%* 42.5% × 10%*	NR
Weder-Cisneros, 2004²⁹	SLE (N = 81) Patients with RA (N = 29)	Face-to-face interview with questionnaire	Yes (ICHD 1)	At least one headache episode within the last year	41% × 17%*	25% × 17%	11% x 0%
Lessa, 2006³⁰	SLE (N = 115) Patients with other rheumatological diseases (N = 92)	Face-to-face interview with questionnaire	Yes (ICHD 1)	At least one headache episode within the last year	75.7% × 66%	66.1% × 52.2%*	13.9% × 16.3%
Guimarães Bettero, 2007³¹	SLE (N = 49) Those accompanying patients (N = 50)	Face-to-face interview with questionnaire	Yes (ICHD 2)	ICHD criteria	85.7% × 56%*	59.2% × 36%*	26.5% × 20%
Harboe, 2009³²	SLE (N = 68) Patients with primary Sjogren syndrome (N = 72)	Face-to-face interview with questionnaire	No	ACR 1999 criteria	87% × 78%	44% × 35%	59% × 56%
Tjensvoll, 2011³³	SLE (N = 67) Hospital workers, friends and neighbors of patients (N = 67)	Face-to-face interview with questionnaire	Yes (ICHD 2)	At least one headache episode within the last year	82% × 72%	36% × 19%*	60% × 58%
Katsiari, 2011³⁴	SLE (N = 72) Controls 1: patients with no autoimmune disease (N = 72) Controls 2: patients with multiple sclerosis (N = 48)	Face-to-face interview with questionnaire	Yes (ICHD 2)	At least one headache episode of any severity within the last 3 years that did not coincide with high fever or infection	50% × 40.3% 50% × 50%	20.8% × 22.2% 20.8% × 22.9%	26.9% × 15.4% 26.9% × 27.1%
Vargas-Hitos, 2014³⁵	SLE (N = 170) Patient relatives and hospital workers (N = 102)	Face-to-face interview plus a review of the medical records	NR	At least one headache episode within the last year	22.4% × 22.5%	NR	NR

Table 1. Summary of controlled studies relating headaches and systemic lupus erythematosus.

Primary author/Year

Sample

Data collection

ICHD

Headache definition

Headache and SLE^a

Migraine and SLE

TTH and SLE

Whitelaw, 2004²⁷

SLE (N = 85)
Emergency nurses (N = 61)

Face-to-face interview with questionnaire

Yes (ICHD 1)

ICHD criteria and questionnaire used

61% × 89%

Appenzeller, 2004²⁸

SLE (N = 85)
Control group 1: patients with RA (N = 40)
Control group 2: patients with no autoimmune disease (N = 40)

Face-to-face interview with questionnaire

Yes (ICHD 1)

Patients with a history of migraine (before the rheumatological disease); a family history of migraine; acute, mild, and non-recurrent headache were excluded

42.5% × 12.5%* 42.5% × 10%*

Weder-Cisneros, 2004²⁹

SLE (N = 81)
Patients with RA (N = 29)

Face-to-face interview with questionnaire

Yes (ICHD 1)

At least one headache episode within the last year

41% × 17%*

25% × 17%

11% x 0%

Lessa, 2006³⁰

SLE (N = 115)
Patients with other rheumatological diseases (N = 92)

Face-to-face interview with questionnaire

Yes (ICHD 1)

At least one headache episode within the last year

75.7% × 66%

66.1% × 52.2%*

13.9% × 16.3%

Guimarães Bettero, 2007³¹

SLE (N = 49)
Those accompanying patients (N = 50)

Face-to-face interview with questionnaire

Yes (ICHD 2)

ICHD criteria

85.7% × 56%*

59.2% × 36%*

26.5% × 20%

Harboe, 2009³²

SLE (N = 68)
Patients with primary Sjogren syndrome (N = 72)

Face-to-face interview with questionnaire

ACR 1999 criteria

87% × 78%

44% × 35%

59% × 56%

Tjensvoll, 2011³³

SLE (N = 67)
Hospital workers, friends and neighbors of patients (N = 67)

Face-to-face interview with questionnaire

Yes (ICHD 2)

At least one headache episode within the last year

82% × 72%

36% × 19%*

60% × 58%

Katsiari, 2011³⁴

SLE (N = 72)
Controls 1: patients with no autoimmune disease (N = 72)
Controls 2: patients with multiple sclerosis (N = 48)

Face-to-face interview with questionnaire

Yes (ICHD 2)

At least one headache episode of any severity within the last 3 years that did not coincide with high fever or infection

50% × 40.3% 50% × 50%

20.8% × 22.2% 20.8% × 22.9%

26.9% × 15.4% 26.9% × 27.1%

Vargas-Hitos, 2014³⁵

SLE (N = 170)
Patient relatives and hospital workers (N = 102)

Face-to-face interview plus a review of the medical records

At least one headache episode within the last year

22.4% × 22.5%

Headache and Systemic Lupus Erythematosus

A Narrative Review

Abstract and Introduction

Abstract

Introduction

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

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