Treatment of thyroid-associated orbitopathy with rituximab--a novel therapy for an old disease: case report and literature review.
OBJECTIVE
To report the use of rituximab to treat thyroid-associated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder-the stiff person syndrome (SPS).


METHODS
We present a case report and a review of the related literature.


RESULTS
A 62-year-old man with SPS, latent autoimmune diabetes of the adult, and Graves-Basedow disease was referred to our medical center because of bilateral TAO. An ophthalmologic examination documented asymmetric bilateral NOSPECS (N = no signs or symptoms; O = only signs, no symptoms; S = soft tissue involvement; P = proptosis; E = extraocular muscle involvement; C = corneal involvement; and S = sight loss) class IV TAO (left eye>right eye) with a clinical activity score of 5 on a scale of 7. Magnetic resonance imaging of the orbits documented bilateral exophthalmos (left eye>right eye) due to retrobulbar fibroadipose infiltration, bilateral increase of extrinsic ocular muscle thickness, and enhancement of the left inferior rectus muscle on T2-weighted sequences. Because of concomitant incapacitating SPS and diet-controlled latent autoimmune diabetes of the adult, we excluded long-term corticosteroid therapy as an option and considered the use of rituximab, a mouse-human chimeric monoclonal antibody targeting the CD20 protein on pre-B and mature B lymphocytes. Rituximab was administered in accordance with the protocol for rheumatoid arthritis. During the subsequent 4 months, clinical signs and symptoms of TAO dramatically resolved (clinical activity score = 0 of 7) with a sustained improvement of the spastic paraparesis. The glutamic acid decarboxylase antibody titer remained high, and glycemic control and first-phase insulin secretion did not change.


CONCLUSIONS
Treatment of active TAO with rituximab should be considered when standard intravenous pulse glucocorticoid treatment is contraindicated or ineffective and when SPS or other organ-specific autoimmune disorders with involvement of humoral autoimmunity are present, inasmuch as more than 1 disease may benefit from the use of this chimeric monoclonal antibody.
Madaschi
Sara
S
Department of Internal Medicine, Endocrinology Unit, San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy.
Rossini
Alessandro
A
Formenti
Ilaria
I
Lampasona
Vito
V
Marzoli
Stefania Bianchi
SB
Cammarata
Gabriella
G
Politi
Letterio S
LS
Martinelli
Vittorio
V
Bazzigaluppi
Elena
E
Scavini
Marina
M
Bosi
Emanuele
E
Lanzi
Roberto
R
D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D000075202:Contraindications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000178:diet therapy / Q000276:immunology; D005938:Glucocorticoids; D049970:Graves Ophthalmopathy / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020336:Paraparesis, Spastic / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D000069283:Rituximab; D016750:Stiff-Person Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D005938:Glucocorticoids; D007155:Immunologic Factors; D000069283:Rituximab