2 41vectors in many innate immune responses [ 46 ]. When both cytokines are in balance,
the result is an equilibrium allowing protective immunity [ 46 ]. TNF-α blockade
results in uninhibited PDC production of IFN-α [ 29 , 31 , 33 , 36 , 43 , 46 ]. When com-
pared to primary plaque psoriasis, patients with anti-TNF-related psoriasis have
been noted to have increased PDCs and IFN-α signaling demonstrated on histologic
specimens [ 31 , 42 , 43 , 47 – 49 ]. Furthermore, psoriasiform lesions have been shown
to develop or worsen after injection of recombinant IFN-α [ 42 ]. IFN-α also height-
ens the expression of chemokine T cell receptors CXCR3, which increases T cell
homing to the skin [ 31 , 36 , 43 , 50 ]. Recruitment of CXCR3 T cells to the skin
results in a T cell-mediated immune response with cytotoxic skin reactions that
leads to the development of psoriasiform skin lesions [ 31 ].
Diagnosis and Management of Psoriasiform and Eczematiform
Lesions
Diagnosis of anti-TNF-related psoriasiform skin lesions requires a thorough history,
physical exam, and possible skin biopsy. It is crucial to exclude trauma, mechanical
stressors, infection, and other medications including beta-blockers, lithium, nonste-
roidal anti-inflammatory drugs, tetracycline, and antimalarials as causative agents
[ 33 , 51 ]. Skin lesions that arise during anti-TNF therapy should be evaluated by a
dermatologist. Lesions that arise in unusual locations such as on the face or at flexor
surfaces may warrant skin biopsy [ 33 ]. Biopsies with immunohistochemical stain-
ing from the anti-TNF-related psoriasiform lesions show increased concentration of
IFN-α in perivascular lymphocytic infiltrate and dermal vasculature [ 36 ]. Other his-
tological findings include epithelial hyperplasia with acanthosis and hyperkeratosis
with increase cell turnover, parakeratosis, lymphocytic infiltration of the epidermis,
and dilated capillaries (see Fig. 14.3) [ 30 , 31 , 33 ].
Fig. 14.3 Psoriasiform
lesion on histology
characterized by epithelial
hyperplasia,
hyperkeratosis, and
lymphocytic infiltration of
the epidermis. Image was
provided by Meghan Gloth,
MD
14 Noninfectious and Nonmalignant Complications of Anti-TNF Therapy