J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 8, Number 7, July 2016, pages 495-505

Comorbidity of Narcolepsy Type 1 With Autoimmune Diseases and Other Immunopathological Disorders: A Case-Control Study

**Table 1.** Autoimmune and Other Immunopathological Diseases Observed in the NT1 Series (N = 158) and Their Prevalence in Spain*
	No. of cases	Frequency (%)	95% CI	Prevalence in Spain
*For some of them, the prevalence observed in some European studies is accepted. CI: confidence interval.
Autoimmune diseases
Multiple sclerosis (MS)	1	0.63	0.01 - 3.4	65/100,000 [27]
Systemic lupus erythematosus (SLE)	1	0.63	0.01 - 3.4	40 - 50/100,000 [28]
Idiopathic thrombocytopenic purpura (ITP)	1	0.63	0.01 - 3.4	Unknown
Psoriasis	2	1.26	0.1 - 4.4	2.3% [29]
Crohn’s disease	2	1.26	0.1 - 4.4	1.9/100,000 [30]
Ulcerative colitis	1	0.63	0.01 - 3.4	8/100,000 [31]
Multinodular goiter autoimmune (MNGA)	1	0.63	0.01 - 3.4	0.8-6.4% (by sex) [32]
Autoimmune thyroid disease (Hashimoto)	2	1.26	0.1 - 4.4	Up to 33% in > 70 years [33]
Celiac disease	1	0.63	0.01 - 3.4	1/370 [34]
Type B insulin resistance syndrome (IRS-B)	1	0.63	0.01 - 3.4	Unknown
Idiopathic recurrent facial palsy (IRFP)	1	0.63	0.01 - 3.4	Unknown
Peyronie’s disease	1	0.63	0.01 - 3.4	Unknown
Antiphospholipid syndrome	1	0.63	0.01 - 3.4	Unknown
Other immunopathological diseases
Allergic rhinitis	12	7.59	3.9 - 12.8	Unknown
Allergic asthma (extrinsic)	6	3.79	1.4 - 8.0	3-7% [26]
Atopic dermatitis	4	2.53	0.6 - 6.3	2-14% [35]
Food allergy	3	1.89	0.3 - 5.4	1-3% (World Health Organization)
Contact dermatitis (heavy metals)	1	0.63	0.01 - 3.4	2-11% (Nickel) [36]

Table 1. Autoimmune and Other Immunopathological Diseases Observed in the NT1 Series (N = 158) and Their Prevalence in Spain*

No. of cases

Frequency (%)

95% CI

Prevalence in Spain

*For some of them, the prevalence observed in some European studies is accepted. CI: confidence interval.

Autoimmune diseases

Multiple sclerosis (MS)

0.63

0.01 - 3.4

65/100,000 [27]

Systemic lupus erythematosus (SLE)

0.63

0.01 - 3.4

40 - 50/100,000 [28]

Idiopathic thrombocytopenic purpura (ITP)

0.63

0.01 - 3.4

Unknown

Psoriasis

1.26

0.1 - 4.4

2.3% [29]

Crohn’s disease

1.26

0.1 - 4.4

1.9/100,000 [30]

Ulcerative colitis

0.63

0.01 - 3.4

8/100,000 [31]

Multinodular goiter autoimmune (MNGA)

0.63

0.01 - 3.4

0.8-6.4% (by sex) [32]

Autoimmune thyroid disease (Hashimoto)

1.26

0.1 - 4.4

Up to 33% in > 70 years [33]

Celiac disease

0.63

0.01 - 3.4

1/370 [34]

Type B insulin resistance syndrome (IRS-B)

0.63

0.01 - 3.4

Unknown

Idiopathic recurrent facial palsy (IRFP)

0.63

0.01 - 3.4

Unknown

Peyronie’s disease

0.63

0.01 - 3.4

Unknown

Antiphospholipid syndrome

0.63

0.01 - 3.4

Unknown

Other immunopathological diseases

Allergic rhinitis

7.59

3.9 - 12.8

Unknown

Allergic asthma (extrinsic)

3.79

1.4 - 8.0

3-7% [26]

Atopic dermatitis

2.53

0.6 - 6.3

2-14% [35]

Food allergy

1.89

0.3 - 5.4

1-3% (World Health Organization)

Contact dermatitis (heavy metals)

0.63

0.01 - 3.4

2-11% (Nickel) [36]

**Table 2.** Demographic and Clinical Characteristics of NT1 Patients With Associated Autoimmune and Other Immunopathological Diseases
	Sex	Age at EDS onset	ESS	Age at cataplexy onset	Frequency of cataplexy (1)	Age at diagnosis of NT1	ADs/IDs	Age at diagnosis of ADs/IDs
Case 1	F	22	23	22	4	32	Idiopathic recurrent facial palsy, autoimmune thyroid disease, antiphospholipid syndrome	12
Case 2	F	7		8	4	8	Allergic rhinitis, food allergy	7
Case 3	M	16	16	53	5	56	Allergic rhinitis	20
Case 4	M	15	16	15	3	30	Peyronie’s disease	30
Case 5	M	17	14	18	5	21	Idiopathic thrombocytopenic purpura	17
Case 6	F	12	15	12	4	27	Multiple sclerosis	26
Case 7	F	29	24	29	5	30	Systemic lupus erythematosus	18
Case 8	M	19	15	21	4	22	Psoriasis	34
Case 9	F	21	16	21	4	22	Allergic asthma, food allergy	16
Case 10	F	6	15	5	5	7	Allergic asthma, food allergy (cow milk)	1
Case 11	M	16	19	16	4	20	Atopic dermatitis, allergic rhinitis	10
Case 12	M	39	17	39	5	42	Allergic asthma
Case 13	F	45	15	45	1	48	Multinodular goiter autoimmune	53
Case 14	F	45	14	47	3	49	Allergic rhinitis	18
Case 15	M	12	19	25	4	19	Psoriasis	10
Case 16	F	9	17	9	5	28	Crohn’s disease, allergic rhinitis	9
Case 17	M	20	19	22	4	26	Allergic rhinitis	9
Case 18	F	10	21	10	5	20	Allergic rhinitis	10
Case 19	F	23		26	5		Allergic rhinitis, contact dermatitis (heavy metals)	14
Case 20	M	25	22	23	4	34	Allergic asthma	15
Case 21	M	23	12	23	4	25	Atopic dermatitis, allergic rhinitis	14
Case 22	F	10	11	17	5		Allergic asthma	21
Case 23	M	27	24	29	4	37	Atopic dermatitis	16
Case 24	M	19	16	20	3	21	Allergic rhinitis	17
Case 25	F	18	17	20	5	51	Ulcerative colitis, autoimmune thyroid disease	36
Case 26	M	17	21	17	5	22	Allergic asthma, allergic rhinitis	10
Case 27	F	7	19	11	5	9	Type B insulin resistance syndrome (IRS-B)	15
Case 28	F	19	17	20	5	25	Crohn’s disease, celiac disease	20
Case 29	F	16	19	18	4	18	Allergic rhinitis	15
Case 30	M	14	20	18	5	67	Atopic dermatitis	22

Table 2. Demographic and Clinical Characteristics of NT1 Patients With Associated Autoimmune and Other Immunopathological Diseases

Sex

Age at EDS onset

ESS

Age at cataplexy onset

Frequency of cataplexy (1)

Age at diagnosis of NT1

ADs/IDs

Age at diagnosis of ADs/IDs

Case 1

Idiopathic recurrent facial palsy, autoimmune thyroid disease, antiphospholipid syndrome

Case 2

Allergic rhinitis, food allergy

Case 3

Allergic rhinitis

Case 4

Peyronie’s disease

Case 5

Idiopathic thrombocytopenic purpura

Case 6

Multiple sclerosis

Case 7

Systemic lupus erythematosus

Case 8

Psoriasis

Case 9

Allergic asthma, food allergy

Case 10

Allergic asthma, food allergy (cow milk)

Case 11

Atopic dermatitis, allergic rhinitis

Case 12

Allergic asthma

Case 13

Multinodular goiter autoimmune

Case 14

Allergic rhinitis

Case 15

Psoriasis

Case 16

Crohn’s disease, allergic rhinitis

Case 17

Allergic rhinitis

Case 18

Allergic rhinitis

Case 19

Allergic rhinitis, contact dermatitis (heavy metals)

Case 20

Allergic asthma

Case 21

Atopic dermatitis, allergic rhinitis

Case 22

Allergic asthma

Case 23

Atopic dermatitis

Case 24

Allergic rhinitis

Case 25

Ulcerative colitis, autoimmune thyroid disease

Case 26

Allergic asthma, allergic rhinitis

Case 27

Type B insulin resistance syndrome (IRS-B)

Case 28

Crohn’s disease, celiac disease

Case 29

Allergic rhinitis

Case 30

Atopic dermatitis

**Table 3.** Results of the Comparative Analysis of the Group of NT1 Patients With ADs/IDs and the Group of NT1 Patients Without ADs/IDs (N = 30)
	NT1, mean ± SD	NT1 + ADs/IDs, mean ± SD	P (Mann-Whitney)
*Pearson χ² test. BMI: body mass index; IR: interquartile range (p25 - p75).
Age	49.6 ± 20.6 (median: 45; IR: 33 - 68)	38 ± 18.3 (median: 36; IR: 28 - 43)	0.071
Sex	16 female (53.3%); 14 male (46.7%)	0.067*
BMI	26.5 ± 4.8 (median: 25.4; IR: 23.4 - 31.2)	26.5 ± 6.3 (median: 25.7; IR: 22.7 - 27.6)	0.811
Epworth sleepiness scale (ESS)	19.1 ± 2.5 (median: 19; IR: 18 - 20)	17.6 ± 3.3 (median: 17; IR: 15 - 20)	0.043
Age at EDS onset	19.6 ± 9.5 (median: 18; IR: 14 - 24)	19.2 ± 9.9 (median: 17.5; IR: 12 - 23)	0.926
Age at diagnosis of AD/ID	-	18.4 ± 11.0 (median: 16; IR: 10 - 21 )	-
Age at onset of cataplexy	23.6 ± 14.8 (median: 20; IR: 14 - 30)	21.9 ± 11.3 (median: 20; IR: 16 - 25)	0.749
Hypnagogic hallucinations (no. of cases and % patients)	15 (50.0%)	17 (56.7%)	0.267*
Sleep paralysis (no. of cases and % patients)	20 (66.6%)	17 (56.6%)	0.634*

Table 3. Results of the Comparative Analysis of the Group of NT1 Patients With ADs/IDs and the Group of NT1 Patients Without ADs/IDs (N = 30)

NT1, mean ± SD

NT1 + ADs/IDs, mean ± SD

P (Mann-Whitney)

*Pearson χ² test. BMI: body mass index; IR: interquartile range (p25 - p75).

Age

49.6 ± 20.6 (median: 45; IR: 33 - 68)

38 ± 18.3 (median: 36; IR: 28 - 43)

0.071

Sex

16 female (53.3%); 14 male (46.7%)

0.067*

BMI

26.5 ± 4.8 (median: 25.4; IR: 23.4 - 31.2)

26.5 ± 6.3 (median: 25.7; IR: 22.7 - 27.6)

0.811

Epworth sleepiness scale (ESS)

19.1 ± 2.5 (median: 19; IR: 18 - 20)

17.6 ± 3.3 (median: 17; IR: 15 - 20)

0.043

Age at EDS onset

19.6 ± 9.5 (median: 18; IR: 14 - 24)

19.2 ± 9.9 (median: 17.5; IR: 12 - 23)

0.926

Age at diagnosis of AD/ID

18.4 ± 11.0 (median: 16; IR: 10 - 21 )

Age at onset of cataplexy

23.6 ± 14.8 (median: 20; IR: 14 - 30)

21.9 ± 11.3 (median: 20; IR: 16 - 25)

0.749

Hypnagogic hallucinations (no. of cases and % patients)

15 (50.0%)

17 (56.7%)

0.267*

Sleep paralysis (no. of cases and % patients)

20 (66.6%)

17 (56.6%)

0.634*

**Table 4.** Comparative Analysis of the Severity of Cataplexy Between the Group of NT1 Patients With ADs/IDs and the Group of NT1 Patients Without ADs/IDs (N = 30)
Severity of cataplexy*	NT1, No. (%)	NT1 + IDs, No. (%)	P
*EU-NN: 1: < 1/year; 2: < 1/month; 3: < 1/week; 4: < 1/day; 5: > 1/day.
Mild to moderate (1, 2, 3)	21 (72.4%)	3 (10%)	< 0.001
Severe (4, 5)	8 (27.6%)	27 (90%)

Table 4. Comparative Analysis of the Severity of Cataplexy Between the Group of NT1 Patients With ADs/IDs and the Group of NT1 Patients Without ADs/IDs (N = 30)

Severity of cataplexy*

NT1, No. (%)

NT1 + IDs, No. (%)

*EU-NN: 1: < 1/year; 2: < 1/month; 3: < 1/week; 4: < 1/day; 5: > 1/day.

Mild to moderate (1, 2, 3)

21 (72.4%)

3 (10%)

< 0.001

Severe (4, 5)

8 (27.6%)

27 (90%)

**Table 5.** Univariate Analysis of Factors Related to the Severity of Cataplexy in the 30 NT1 Patients With ADs/IDs and the 30 NT1 Patients Without ADs/IDs (N = 60)
Severity of cataplexy*	Mild to moderate (1, 2, 3)	Severe (4, 5)	OR	95% CI for OR
*EU-NN: 1: < 1/year; 2: < 1/month; 3: < 1/week; 4: < 1/day; 5: > 1/day. OR: odds ratio; CI: confidence interval.
Sex			1.12	0.39 - 3.20
Male	42.3%	57.7%
Female	39.4%	60.6%
Age (years)	53.5 ± 20.2	37.1 ± 17.9	0.95	0.92 - 0.98
Presence of IDs			23.6	5.5 - 100.1
No	72.4%	27.6%
Yes	10%	90%
Epworth (ESS)	18.4 ± 2.5	18.2 ± 3.4	0.98	0.82 - 1.17
Age at cataplexy onset (years)	28 ± 16.3	19.2 ± 9.3	0.94	0.90 - 0.99

Table 5. Univariate Analysis of Factors Related to the Severity of Cataplexy in the 30 NT1 Patients With ADs/IDs and the 30 NT1 Patients Without ADs/IDs (N = 60)

Severity of cataplexy*

Mild to moderate (1, 2, 3)

Severe (4, 5)

95% CI for OR

*EU-NN: 1: < 1/year; 2: < 1/month; 3: < 1/week; 4: < 1/day; 5: > 1/day. OR: odds ratio; CI: confidence interval.

Sex

1.12

0.39 - 3.20

Male

42.3%

57.7%

Female

39.4%

60.6%

Age (years)

53.5 ± 20.2

37.1 ± 17.9

0.95

0.92 - 0.98

Presence of IDs

23.6

5.5 - 100.1

72.4%

27.6%

Yes

10%

90%

Epworth (ESS)

18.4 ± 2.5

18.2 ± 3.4

0.98

0.82 - 1.17

Age at cataplexy onset (years)

28 ± 16.3

19.2 ± 9.3

0.94

0.90 - 0.99

**Table 6.** Autoimmune and Other Immunopathological Diseases Observed in the Control Group of General Population (N = 151)
	Number of cases	Frequency (%)	95% CI
CI: confidence interval.
Autoimmune diseases
Psoriasis	1	0.66	0.01 - 3.6
Ulcerative colitis	1	0.66	0.01 - 3.6
Autoimmune thyroid disease (Hashimoto)	2	1.32	0.02 - 4.7
Other immunopathological diseases
Allergic rhinitis	12	7.94	4.1 - 13.4
Allergic asthma (extrinsic)	2	1.32	0.02 - 4.7
Atopic dermatitis	2	1.32	0.02 - 4.7
Food allergy	1	0.66	0.01 - 3.6

Table 6. Autoimmune and Other Immunopathological Diseases Observed in the Control Group of General Population (N = 151)

Number of cases

Frequency (%)

95% CI

CI: confidence interval.

Autoimmune diseases

Psoriasis

0.66

0.01 - 3.6

Ulcerative colitis

0.66

0.01 - 3.6

Autoimmune thyroid disease (Hashimoto)

1.32

0.02 - 4.7

Other immunopathological diseases

Allergic rhinitis

7.94

4.1 - 13.4

Allergic asthma (extrinsic)

1.32

0.02 - 4.7

Atopic dermatitis

1.32

0.02 - 4.7

Food allergy

0.66

0.01 - 3.6

**Table 7.** Comparative Analysis Between the Group of NT1 Patients and the Control Group of General Population (N = 151)
	NT1 patients, No. (%)	Controls, No. (%)	P (Pearson χ²)	RR	OR	95% CI for OR
RR: relative risk; OR: odds ratio; CI: confidence interval.
ADs	12 (7.95%)	4 (2.65%)	0.040	3.00	3.17	1.01 - 10.07
Other IDs	19 (12.58%)	16 (10.60%)	0.590	1.19	1.21	0.59 - 2.46
All	29 (19.21%)	18 (11.92%)	0.081	1.61	1.75	0.92 - 3.32

Table 7. Comparative Analysis Between the Group of NT1 Patients and the Control Group of General Population (N = 151)

NT1 patients, No. (%)

Controls, No. (%)

P (Pearson χ²)

95% CI for OR

RR: relative risk; OR: odds ratio; CI: confidence interval.

ADs

12 (7.95%)

4 (2.65%)

0.040

3.00

3.17

1.01 - 10.07

Other IDs

19 (12.58%)

16 (10.60%)

0.590

1.19

1.21

0.59 - 2.46

All

29 (19.21%)

18 (11.92%)

0.081

1.61

1.75

0.92 - 3.32