Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone.

Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA) may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs) or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable") RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a disease-modifying anti-rheumatoid drug (DMARD) and an anti-TNF-α agent (infliximab or etanercept) to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N = 122), unstable DMARD patients (N = 18), stable DMARD patients (N = 26), and stable patients on combination therapy (N = 20). Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

Failure of extensive extramammary Paget disease of the inguinal area to clear with imiquimod cream, 5%: possible progression to invasive disease during therapy.

BACKGROUND: Surgical approaches are the standard treatment for extramammary Paget disease (EMPD), but nonsurgical modalities may be preferred and more appropriate for some patients. Topical administration of imiquimod cream, 5%, has improved or resolved in situ EMPD (n = 21), but treatment failures (n = 6) have also been reported. OBSERVATIONS: We treated an elderly patient with initial biopsy-proved in situ genital EMPD with daily topical imiquimod, 5%, for 14 weeks. Midtreatment mapping biopsy specimens demonstrated invasive disease, with minimal clinical improvement. The patient subsequently underwent surgical excision. CONCLUSIONS: Of the 27 published cases that describe imiquimod treatment of EMPD, 6 report treatment failure (22%), but factors that may contribute to treatment failure are not well understood. In the present patient, treatment with imiquimod may have been complicated by variable lesion thickness, which inhibited uniform penetration of imiquimod, or the presence of invasive disease not detected on initial biopsy. The efficacy of imiquimod to treat extensive invasive EMPD has not been demonstrated, and surgical approaches remain the most appropriate treatment for invasive disease. Variable responses to topical imiquimod use among patients suggest that other factors may be important in determining response to therapy.

Improvement of nonbullous congenital ichthyosiform erythroderma following functional endoscopic sinus surgery.

We report the case of a child with congenital nonbullous ichthyosiform erythroderma on long-term isotretinoin who developed progressively worsening ichthyosis along with recurrent bouts of sinusitis. Endoscopic sinus surgery revealed osteophytes, most likely an isotretinoin-related adverse event, and post operatively the patient's sinus disease and skin disease both dramatically improved. This case represents the first report, to our knowledge, of ichthyosis improving after endoscopic sinus surgery.