Evidence of impaired sense of smell in hereditary angioedema.
BACKGROUND
Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE.


METHODS
Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment.


RESULTS
A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly.


CONCLUSIONS
Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect.
Perricone
C
C
Reumatologia, Dipartimento di Clinica e Terapia Medica, Sapienza Università di Roma, Rome, Italy. carlo.perricone@gmail.com
Agmon-Levin
N
N
Shoenfeld
N
N
de Carolis
C
C
Guarino
M D
MD
Gigliucci
G
G
Milana
I
I
Novelli
L
L
Valesini
G
G
Perricone
R
R
Shoenfeld
Y
Y
D000328:Adult; D054179:Angioedemas, Hereditary / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D016022:Case-Control Studies; D050718:Complement C1 Inhibitor Protein / Q000235:genetics; D003181:Complement C4 / Q000378:metabolism; D015941:Complement Hemolytic Activity Assay; D003171:Complement Pathway, Classical; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000857:Olfaction Disorders / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D012903:Smell / Q000502:physiology*
D050718:Complement C1 Inhibitor Protein; D003181:Complement C4