Objective To report our experience using mycophenolate mofetil as first-line treatment for dermatomyositis-associated interstitial lung disease. Methods We examined the medical records of all 16 dermatomyositis patients with interstitial lung disease seen in our outpatient university hospital dermatology clinic between May 26, 2006 and May 25, 2009. In this retrospective case series, we describe the clinical course of the four patients with definitive evidence of interstitial lung disease on radiologic imaging who were treated with mycophenolate mofetil and had pulmonary data available to document their outcome. All patients also received prednisone. Results All three patients with at least one year of follow-up on mycophenolate mofetil experienced complete normalization of pulmonary function tests (including diffusing capacity for carbon monoxide) and resolution of dyspnea. They were also able to reduce their prednisone doses. The only patient with pre- and post-treatment chest computed tomography imaging had total resolution of her interstitial opacities. The patient with only five months of post-treatment follow-up experienced an improvement in diffusing capacity for carbon monoxide from 44 to 77% predicted but no change in dyspnea. Conclusion These promising data indicate that mycophenolate mofetil may be a useful therapy for interstitial lung disease in dermatomyositis patients, but larger studies are needed to more definitively evaluate this medication’s role in therapy.

Inhibition of DNA replication with hydroxyurea during thymine starvation of Escherichia coli shows that active DNA synthesis is not required for thymineless death (TLD). Hydroxyurea experiments and thymine starvation of lexA3 and uvrA DNA repair mutants rule out unbalanced growth, the SOS response, and nucleotide excision repair as explanations for TLD.Thymineless death (TLD), the phenomenon in which exponentially growing cells starved for thymine lose viability, has been researched for over five decades, but the molecular mechanism remains an enigma. Thymine starvation halts DNA synthesis; Maaløe and Hanawalt (9) proposed a connection between stalled replication forks and TLD in Escherichia coli after showing that only those cells actively replicating DNA when thymine was removed underwent TLD (8). To test the role of replication in TLD, we examined the impact of various concentrations of hydroxyurea (HU) on the viability of E. coli cells starved for thymine. HU specifically inhibits replication by preventing the function of ribonucleoside diphosphate reductase, thus starving the cell for all four deoxynucleotides. At high concentrations, HU also significantly inhibits transcription by an unexplained mechanism, but at low concentrations, the effects of HU appear to be largely limited to inhibition of DNA replication (14).HU exposure affected TLD in a concentration-dependent manner. The protection against TLD afforded by HU increased with increasing concentrations of HU. The thyminerequiring E. coli strain HL813 (all strains used in this study are listed in Table 1) was grown overnight at 37°C in Difco Davis minimal medium containing 0.4% glucose and 0.1% Casamino Acids (DM medium) supplemented with 10 g/ml thymine. The overnight culture was diluted in the same medium and grown at the same temperature with shaking. During the exponential phase (10 6 to 10 8 cells/ml), cells were collected on a Millipore filter (pore size, 0.45 m) and washed and resuspended in DM medium without thymine. HU was added to the specified bacterial cultures at the designated final concentration, and at the indicated time intervals 0.01-ml aliquots were removed, appropriately diluted, and plated on DM agar plates supplemented with 10 g/ml thymine for the determination of viability. When 200 mM HU was added to thymine-starved cells, viable cell counts remained constant over a 4-h time period (Fig. 1a). However, TLD was observed at lower concentrations of HU, albeit at a slightly lower rate than in the control without HU (Fig. 1b and c). At higher HU concentrations, such as 200 mM, RNA synthesis was greatly reduced (Fig. 2a). Since inhibition of RNA synthesis protects against TLD (4, 6, 10), it is likely that the lack of TLD at 200 mM HU is mostly due to inhibition of RNA synthesis. However, inhibition of DNA synthesis could also be involved in the TLD protection, because DNA synthesis was completely inhibited in the presence of 200 mM HU (Fig. 2b). On the other hand, although DNA synthesis was inhibited more than 90% at the lowest concen...

This article provides an overview of cutaneous lupus erythematosus (CLE), including classification schemes, disease subtypes, and therapy. It also describes a novel clinical outcome instrument called the Cutaneous Lupus Erythematosus Disease Area and Severity Index, which quantifies cutaneous activity and damage in CLE. KeywordsCutaneous lupus erythematosus; disease classification; Rowell's syndrome; CLASI; clinical outcome instrument OVERVIEW OF CUTANEOUS LUPUS ERYTHEMATOSUS Disease ClassificationCutaneous LE skin lesions have been divided into two categories based on histopathology, LE-specific (histopathology shows interface dermatitis, which is specific for LE) and LEnonspecific (no interface dermatitis, histopathology is not specific for LE) [1,2]. The diagnosis of cutaneous LE can be confirmed by the presence of LE-specific lesions, whereas LE-nonspecific lesions may be seen in several diseases and thus are not sufficient for establishing a diagnosis of cutaneous LE. LE-specific skin lesions can be further subdivided based on clinical characteristics into acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE) [2]. Table 1 [ [2][3][4] summarizes the classification of skin lesions seen in LE patients.The risk of systemic LE (SLE) is highest in ACLE and lowest in CCLE, with SCLE falling in between. In one study of 191 patients with LE-specific skin lesions, the prevalence of underlying SLE was 72% in all patients with ACLE lesions, 58% in all patients with SCLE lesions, 28% in all patients with DLE lesions (the most common type of CCLE), and 6% in all patients with localized DLE lesions (limited to the head and neck) [5]. Notably, many patients from this study had lesions from more than one clinical category (ACLE, SCLE, or CCLE), and some had lesions from all three categories. In patients with DLE lesions but no ACLE or SCLE lesions, the underlying prevalence of SLE was 15%.Corresponding author for proof and reprints: Dr. Victoria P. Werth Department of Dermatology Perelman Center for Advanced Medicine, Suite 1-330A 3400 Civic Center Boulevard Philadelphia, PA 19104 Tel. 215-823-4208, Fax 866-755- Approximately 50% of SCLE patients fulfill the criteria for SLE [5], but SLE patients with SCLE appear to have fewer organ systems involved than SLE patients without SCLE. One study that compared inpatients with both SLE and SCLE to inpatients with only SLE found an increased prevalence of central nervous system disease, renal disease, arthritis, anemia, and pleuritis in the SLE-only group [24]. Another study that compared outpatients with SCLE (some also had SLE) to outpatients with SLE alone found an increased frequency of serositis (pleuritis or pericarditis) and hematologic abnormalities (hemolytic anemia, thrombocytopenia, or leukopenia) in the SLE-only group [25].Although drug-induced DLE is very rare, numerous drugs have been reported to induce SCLE. Drug-induced SCLE resembles idiopathic SCLE both clinically (papulosquamous or annular-polycyclic photodistributed les...

Objectives:(1) To determine the prevalence of interstitial lung disease (ILD) and isolated low diffusing capacity for carbon monoxide (DLCO) in a large cohort of outpatients with dermatomyositis. (2) To compare the pulmonary abnormalities of patients with classic dermatomyositis and those with skin-predominant dermatomyositis.