243Lupus-Like Syndrome
Clinical Presentation
Lupus-like syndrome (LLS), a rare autoimmune disorder, is a recognized adverse
reaction to anti-TNF therapy in IBD patients [ 52 ]. Compared to systemic lupus
erythematosus (SLE), patients with LLS tend to be older with mean age of
46–51 years, and with slight female predominance [ 53 – 55 ]. LLS is generally char-
acterized by arthralgia, myalgia, fever, arthritis, and serositis [ 52 , 55 ]. While malar
rash, photosensitivity, and oral ulcers are less common in LLS [ 55 ], skin involve-
ment and photosensitivity are common in patients who develop LLS after anti-TNF
therapy [ 54 , 56 , 57 ]. However, central nervous system and renal involvement are
rarely seen in LLS [ 55 , 56 ].
Patients who have received anti-TNF therapy are at high risk of developing auto-
antibodies [ 57 , 58 ], but the rate of LLS is generally low at 0.5–1% [ 59 , 60 ]. In the
ACCENT I trial consisting of 573 patients randomized to placebo or infliximab,
positive antinuclear antibodies (ANA) and double-stranded (ds) DNA were more
common in patients on infliximab than those on placebo, 56% and 34% vs. 35% and
11%, respectively [ 12 ]. However, only two patients in the infliximab groups with
positive autoantibodies developed LLS [ 12 ]. Similarly, in a multicenter, longitudi-
nal, observational study where 286 patients had autoantibodies assessed both before
and after at least 6 months of infliximab treatment, only one patient (0.35%) in this
cohort was diagnosed with LLS [ 57 ].
Autoantibodies are also common after treatment with adalimumab. In a case
series consisting of 180 IBD patients treated with an anti-TNF therapy (inflix-
imab or adalimumab, or infliximab and adalimumab consecutively), 44.4% were
found to have antinuclear antibody (ANA) titers ≥1:240, and 15.6% had dsDNA
serum levels ≥9 U/mL [ 52 ]. Only 1.1% of these patients, however, had severe
LLS requiring immediate discontinuation of anti-TNF therapy. Severe LLS was
defined as severe arthralgia including joint swelling and/or additional LLS-
related symptoms requiring immediate discontinuation of anti-TNF therapy and
initiation of corticosteroids and/or immunosuppressive therapy [ 52 ]. Biegel et al.
observed that the ANA and dsDNA titers positively correlate with clinical sever-
ity of LLS [ 52 ].
Table 14.3 Management of anti-TNF-induced psoriasiform lesions
Mild Severe
Topical corticosteroid Discontinuation of anti-TNF therapy
Emollients Topical therapy (as for mild disease)
Keratolytic therapy Phototherapy (as for mild disease)
Vitamin D analogs Retinoids
Ultraviolet phototherapy Methotrexate
Cyclosporine14 Noninfectious and Nonmalignant Complications of Anti-TNF Therapy