agents. Granulomas are composed predominantly of mononu-
clear cell with lymphocytes and macrophages secreting TNF-α
and interferon-gamma. Moreover, some investigations have
shown that an overexpression of TNF-α by peripheral mono-
nuclear lymphocytes and macrophages may play a role in the
development of GA.6 Therefore, interfering with TNF-α can lead
to breakdown of the granuloma structure.
Adalimumab is a fully human anti-TNF-α monoclonal antibody
that binds specifically to soluble and membrane-bound TNF-α,
blocking its interaction with p55 and p75 cell surface TNF recep-
tors. Adalimumab is currently approved for psoriasis, juvenile
rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis,
adult rheumatoid arthritis, and Crohn's disease. Adalimumab,
like infliximab, inhibits not only soluble TNF-α but also trans-
membrane TNF-a, while etanercept mainly binds soluble TNF-α.7
The ability to adalimumab and infliximab to bind transmem-
brane TNF-α may explain why adalimumab and infliximab—but
not etanercept—induce apoptosis of monocytes and T-lympho-
cytes in Crohn's disease.8
This partially different mechanism of the TNF-α inhibition be-
tween etanercept and anti-TNF-α monoclonal antibodies might
justify the lower clinical efficacy of etanercept, but not infliximab
and adalimumab, in the treatment of granulomatous diseases
as Crohn's disease and Wegener's granulomatosis, and the
more pronounced propensity of the monoclonal antibodies in
comparison with etanercept in reactivation of latent tubercu-
losis. It could also explain the treatment failure of 4 patients
with GGA treated with etanercept reported by Kreuter et al.9 In
fact, several recent reports have demonstrated that infliximab
was highly effective in the treatment of other granulomatous
skin disorders such as cutaneous sarcoidosis and necrobiosis
lipoidica, which are sometimes difficult to treat.
This case is another example that anti-TNF-α inhibitors (mainly
the monoclonal antibodies adalimumab and infliximab) be-
cause of their slightly different mechanism of action relatively
to etanercept, should be considered a therapeutic option in re-
The authors have no relevant conflicts of interest to disclose
- Smith MD, Downie JB, DiCostanzo D. Granuloma annulare. Int J Dermatol. 1997;36:326-333.
- Hertl MS, Haendle I, Schuler G, Hertl M. Rapid improvement
of recalcitrant disseminated granuloma annulare upon treat-
ment with the tumor necrosis factor-alpha inhibitor, inflix-
imab. Br J Dermatol. 2005;152:552-555.
- Shupack J, Siu K. Resolving granuloma annulare with etaner-
cept. Arch Dermatol. 2006;142:394-395.
- Knoell KA. Efficacy of adalimumab in the treatment of gener-
alized granuloma annulare in monozygotic twins carrying the
8.1 ancestral haplotype. Arch Dermatol. 2009;145:610-611.
- Rosmarin D, LaRaia A, Schlauder S, Gottlieb AB. Successful treat-
ment of disseminated granuloma annulare with adalimumab. J Drugs Dermatol. 2009;8:169-171.