Fatal paraneoplastic pemphigus associated with a mediastinal tumor.

Paraneoplastic pemphigus (PNP) is a rare life-threatening autoimmune bullous skin disease which is an obligate paraneoplasma. A 34-year-old woman presented with recalcitrant stomatitis and a generalized lichenoid rash. A diagnosis of PNP was established based on clinical findings, immunofluorescence, histopathology and biochemistry. A localized mediastinal mass was found with CT imaging and excised. The histologic diagnosis was dendritic cell sarcoma. Despite removal of tumor and immunosuppressive therapy, the PNP progressed rapidly and the patient died of septic multiorgan failure.

Autoantibodies to the translational suppressors T cell intracytoplasmic antigen 1 and T cell intracytoplasmic antigen 1-related protein in patients with rheumatic diseases: increased prevalence in systemic lupus erythematosus and systemic sclerosis and correlation with clinical features.

OBJECTIVE: T cell intracytoplasmic antigen 1 (TIA-1) and TIA-1-related protein (TIAR) are involved in posttranscriptional regulation of the expression of tumor necrosis factor alpha (TNFalpha) and other proteins. Given the pivotal role of TNFalpha in chronic inflammatory diseases, this study was undertaken to analyze sera from patients with systemic autoimmune diseases for the presence of autoantibodies to TIA proteins and to investigate the expression of these proteins in inflamed tissue. METHODS: The presence of autoantibodies to TIA proteins in sera from 385 patients with rheumatic diseases and healthy controls was determined by immunoblotting using recombinant antigens. Expression of TIA proteins in skin and kidney tissue was analyzed by immunohistochemistry. Serum levels of TNFalpha were measured by enzyme-linked immunosorbent assay. RESULTS: Autoantibodies to TIA-1 and/or TIAR were detected in 61% of patients with systemic lupus erythematosus (SLE), 42% of patients with systemic sclerosis (SSc), 15-31% of patients with other rheumatic diseases, and 6% of healthy controls. Compared with patients negative for anti-TIA antibody, anti-TIA antibody-positive SLE patients had higher disease activity (P = 0.01), elevated antibodies to double-stranded DNA (P = 0.0003), and increased serum TNFalpha levels (P = 0.018). In SLE patients, anti-TIAR antibodies were associated with lupus nephritis (P = 0.02), while in patients with SSc, anti-TIA-1 was associated with lung involvement (P = 0.02). Immunohistochemical analysis of skin and kidney tissue revealed aberrant expression of TIA proteins in skin lesions from SLE and SSc patients, as well as in glomerular cells from SLE patients. CONCLUSION: Aberrant expression of TIA proteins in inflammatory tissue may lead to systemic autoantibody responses, particularly in SLE and SSc. Increased occurrence of anti-TIA autoantibodies in patients with severe organ involvement may point to a possible pathogenetic role.

Combination of an EGFR blocker and a COX-2 inhibitor for the treatment of advanced cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers worldwide. Epidermal growth factor receptor (EGFR) is expressed at the cell surface by more than 90% of SCCs and its activation is responsible for cell cycle progression, proliferation, survival, angiogenesis and metastasis. Cyclooxygenase-2 (COX-2) is an enzyme up-regulated through EGFR signaling and responsible for some of the EGFR-dependent biological effects. An 88-year-old man presented with a recurrent, locoregionally meta-static SCC of the right parietal region, which was resistant to radiotherapy. With a combination therapy of an EGFR blocker (cetuximab) and a COX-2 inhibitor (celecoxib), the tumor regressed partially and the patient's Karnofsky index improved. We speculate that the combined use of cetuximab and COX-2 inhibitors can be a new and effective therapy for advanced and recurrent cutaneous SCCs.

Soluble FAS ligand: a discriminating feature between drug-induced skin eruptions and viral exanthemas.

The clinical spectrum of cutaneous eruptions comprises benign variants like maculopapular rashes (MPRs) and potentially life-threatening events such as toxic epidermal necrolysis (TEN). Apoptosis of keratinocytes is a common histopathological feature of all these drug eruptions. As in skin lesions of TEN and Stevens-Johnson syndrome patients, apoptosis of keratinocytes is often accompanied by an only sparse cellular infiltrate, a soluble fatty acid synthetase ligand (sFASL)-mediated mechanism of keratinocyte cell death is postulated. In MPR patients, evidence for the occurrence of a similar process could not be established so far. We therefore examined sera and lesional skin sections from patients with clinical variants of drug eruptions for FASL expression using a sandwich ELISA and immunohistochemistry, respectively. As controls, healthy persons and patients with other inflammatory skin diseases such as viral exanthema were analyzed. Elevated levels of FASL were detected not only in TEN patients but also in sera and lesional skin of patients with MPR. In contrast, sFASL was repeatedly negative in all viral exanthemas and healthy controls tested. Thus, determination of sFASL serum concentration may represent a discriminating tool between drug rashes and viral exanthemas.

IgA pemphigus--occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody reactivity in an individual patient.

BACKGROUND: IgA pemphigus is a rare pustular autoimmune disease with exclusive IgA anti-keratinocyte cell surface antibody reactivity. Two subtypes have been discerned: in the subcorneal pustular dermatosis type, desmocollin 1 has been identified as a targeted autoantigen, while in few cases of the intraepidermal neutrophilic type, IgA anti-desmoglein 1 or IgA anti-desmoglein 3 reactivity has been demonstrated. PATIENTS AND METHODS: A 48-year-old white male presented with generalized large confluent pustules. Skin pathology was assessed by histology and direct immunofluorescence analysis. IgG/IgA autoantibodies against desmoglein 1/3 and desmocollin 1 were measured by ELISA and indirect immunofluorescence using desmocollin 1 cDNA-transfected COS7 cells, respectively. RESULTS: Histopathology revealed subcorneal pustules and direct immunofluorescence microscopy exclusively showed in vivo bound IgA with an intercellular pattern in the epidermis. Desmocollin 1 was identified as a target of IgA autoantibodies by indirect immunofluorescence microscopy utilizing desmocollin 1 cDNA-transfected COS7 cells. In addition, IgA anti-desmoglein 1 reactivity was demonstrated by ELISA. Neither IgA anti-desmoglein 3 nor IgG anti-desmoglein 1/3 autoantibodies were present. CONCLUSIONS: Both desmocollin 1 and desmoglein 1 were autoantigens in this patient with IgA pemphigus and a distinct clinical presentation. To our knowledge, this is the first IgA pemphigus case with dual autoantibody reactivity.