Histopathologic spectrum of psoriasiform skin reactions associated with tumor necrosis factor-α inhibitor therapy. A study of 16 biopsies.

Tumor necrosis factor (TNF)-α inhibitors (anti-TNF-α biologic drugs), currently used to treat different autoimmune conditions, may be associated with cutaneous drug reactions. New onset or worsening of psoriasis and psoriasis-like reactions have been reported in these patients. However, not much is known about the different histopathologic patterns of such skin lesions. The aim of this study was to evaluate the pathologic spectrum of clinically papulosquamous to pustular "psoriasiform" lesions in this setting. Sixteen biopsies from 9 patients on anti-TNF-α therapy for rheumatoid arthritis (n = 7), Crohn disease (n = 1), and Behçet disease (n = 1) who developed a "psoriasiform" skin rash during treatment were included in this study. None of the patients had history of psoriasis. Five patients (10 biopsies) showed a psoriasis-like pattern that varied from that seen in guttate lesions (4 biopsies), to well-established plaques (3 biopsies) to pustular psoriasis (3 biopsies). Three patients (4 biopsies) showed an interface/lichenoid dermatitis mimicking lichen planus. Two patients (2 biopsies) showed features of pustular folliculitis. Eosinophils varied from none (2 biopsies) to scattered (7 biopsies) to numerous (7 biopsies). Plasma cells were present in most cases. All pustular lesions had negative cultures. In conclusion, anti-TNF drugs elicit a spectrum of cutaneous reactions that go beyond the classical eosinophilic-rich hypersensitivity reaction and may closely mimic primary dermatitis. In addition to psoriasis-like lesions, lichen planus-like dermatitis and sterile pustular folliculitis should be included in the list of anti-TNF-α-related drug reactions. Because the different histopathologic findings may be subtle, clinical correlation is crucial to make the diagnosis.

Mitochondrial DNA deletions serve as biomarkers of aging in the skin, but are typically absent in nonmelanoma skin cancers.

The potential role of mitochondrial DNA (mtDNA) deletions in nonmelanoma skin cancer (NMSC) and in cutaneous photoaging was explored using a genetic approach. Tumors and photodamaged tumor-free "margin" skin were obtained from NMSC patients undergoing excision and the mtDNA from these specimens was screened for the presence of deletions using long extension PCR. mtDNA deletions were abundant in margin tissue specimens from older patients and their number correlated with the patient age. There was a statistically significant difference between the number of mtDNA deletions in tumors and margins. Fewer deletions were detected in the tumors than the margins and the tumors often had no deletions, implying a potential selection for full-length mtDNA or perhaps a protective role for mtDNA deletions in the process of tumorigenesis. The observed mtDNA deletions from skin were often unreported (19 of 21 deletions), but typically shared structural features with mtDNA deletions reported in other tissues. Some mtDNA deletions were detected from the skin of multiple individuals, including 3,715 and 6,278-base pair (bp) deletions, whose frequencies approached that of the previously well-characterized 4977-bp "common" deletion. These data support the use of mtDNA mutations as biomarkers of photoaging in the skin.

High-throughput mitochondrial genome screening method for nonmelanoma skin cancer using multiplexed temperature gradient capillary electrophoresis.

BACKGROUND: We explored the utility of multiplexed temperature gradient capillary electrophoresis (TGCE) as a screening tool for identifying genetic changes in the human mitochondrial genome. We examined changes in mitochondrial DNA (mtDNA) in nonmelanoma skin cancers (NMSCs), using TGCE to resolve genetic differences contained within the tumors compared with the control DNA. METHODS: The entire mtDNA from NMSC tissue samples was amplified in 17 overlapping amplicons averaging 1.1 kb in size. Fourteen of these amplicons were digested with restriction endonucleases into as many as five smaller analyzable fragments. Digested tumor mtDNA amplicons were annealed with digested amplicons from the control DNA to form heteroduplexes in regions of DNA mismatch. TGCE was performed in a 96-well parallel format to detect mtDNA changes in a high-throughput fashion. RESULTS: TGCE resolved heteroduplexes from homoduplexes in singlet reactions and in multiplexed assays. Using a single programmed temperature gradient, we detected 18 of 20 mtDNA changes contained within the specimens. This system was also able to detect a single nucleotide change in a fragment as large as 2 kb. CONCLUSION: Multiplexed TGCE is a sensitive and high-throughput screening tool for identifying mtDNA variations.