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Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. We sought to assess efficacy and safety of ustekinumab in patients with moderate-to-severe AD. In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16 weeks, and last dose at 32 weeks. Background therapy with mild topical steroids was allowed to promote retention. Study endpoints included clinical (SCORAD50) and biopsy-based measures of tissue structure and inflammation, using protein and gene expression studies. The ustekinumab group achieved higher SCORAD50 responses at 12, 16 (the primary endpoint) and 20 weeks compared to placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 32 weeks in the initial ustekinumab group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen after 4 weeks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-γ, elafin/PI3, CXCL1 and CCL17; P

Topical glucocorticosteroids are considered an efficient treatment option for atopic dermatitis (AD), but a global assessment of glucocorticosteroid responses on key disease circuits upon weeks to months of treatment is currently lacking.We sought to assess short (4 weeks) and long-term (16 weeks) application of topical glucocorticosteroids on AD skin and define response biomarkers.The effects of triamcinolone acetonide cream 0.025% were assessed based on gene expression and immunohistochemistry studies at baseline, 4 weeks, and 16 weeks in biopsy specimens from 15 patients with moderate-to-severe AD.At 16 weeks, only 3 patients were clinical responders (by using SCORAD50 criteria), but 6 patients qualified as responders based on histologic criteria. Baseline characteristics indicated more severe disease in nonresponders. While 3 of 15 patients experienced only transient benefit after 4 weeks, others showed progressive improvements toward 16 weeks. Topical glucocorticosteroid use in patients with AD resulted in improvements of the AD genomic signature of 25.6% at 4 weeks and 71.8% at 16 weeks, respectively, and even 123.9% in the histologic responder group. Cytokines (IL-12p40, IL-13, IL-22, CCL17, CCL18, peptidase inhibitor 3 [PI3]/elafin, and S100As) showed consistent decreases from baseline toward 16 weeks with corresponding improvements in epidermal disease hallmarks (keratin 16 and loricrin) in lesional skin from responders (P .05). Nonresponders largely showed lesser/nonsignificant reductions in key inflammatory and barrier markers (keratin 16, IL-13, IL-22, CCL17, CCL18, PI3/elafin, S100As, and loricrin). The combination of IL-21 and IFN-γ baseline expression closely predicted individual clinical glucocorticosteroid responses at 16 weeks of treatment.Our study indicates that even low-potency glucocorticosteroids can broadly affect immune and barrier responses in patients with moderate-to-severe AD, associating higher baseline severity with increased steroid resistance in patients with AD.

TNF inhibitors have been proven to be effective in treating psoriatic arthritis, however not every patient responds to or tolerates treatment. Between 20% and 40% of patients are switched to a different TNF inhibitor, and 5% to 15% are eventually treated with three different TNF inhibitors. Loss of efficacy is the most common reason patients fail TNF inhibitor therapy, followed by adverse effects. Less than a quarter of patients who switched TNF inhibitors did so due to lack of primary response. The majority of data demonstrates that switching can be clinically beneficial after failure of one TNF inhibitor, but is associated with lower response rates compared to initial treatment. Drug survival rates also decrease with multiple courses of treatment. If a psoriatic arthritis patient fails two TNF inhibitors, it may be more efficacious to switch to one of the newer biologics with an alternate mechanism of action.

Subacute cutaneous lupus erythematosus (SCLE) is a form of cutaneous lupus erythematosus that is characterized by nonscarring, erythematous, annular eruptions occurring mainly on sun-exposed areas. The incomplete understanding of SCLE creates challenges in diagnosis and treatment. This report describes the rare case of SCLE co-existing with plaque psoriasis.

Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.

Intravenous immunoglobulins (IVIGs) are beneficial and safe for various diseases other than primary immunodeficiencies. Over the years, IVIG has been given for autoimmune diseases as an off-label adjunct therapy. While other biologic agents are indicated for rheumatoid arthritis (RA), IVIG may have a role for specific subgroups of RA patients where anti-cytokine blockers or rituximab may be unwarranted. Such subgroups may include patients with vasculitis, overlap rhupus syndrome, severe infections with active disease, and pregnancy. In addition, IVIG may be considered for juvenile chronic arthritis (JCA) and adult Still's disease. We review the literature for IVIG treatment in RA patients and for these subgroups.

There are many factors that determine the type of vehicle chosen for a topical medication. Physician considerations include the body region where the agent will be applied, the thickness of the skin, and the amount of surface area in question. Patient considerations include ease of application and removal and aesthetic appeal. We compared the spreadability of five delivery systems used for topical medications (cream, lotion, ointment, gel, and foam) on five types of surfaces (synthetic skin, cardboard, aluminum foil, hard plastic, and soft plastic). In our study (for a set quantity of medication), the foam had the highest spreadability on all tested surfaces, and the ointment the lowest, with the foam covering nine times the surface area of the ointment. This quality makes foam agents ideal for large surface areas. Spreadability can help improve patient tolerability and compliance.

Background IL-22 is potentially a pathogenic cytokine in patients with atopic dermatitis (AD), but the molecular effects of IL-22 antagonism have not been defined in human subjects. Objective We sought to evaluate the cellular and molecular effects of IL-22 blockade in tissues from patients with moderate-to-severe AD. Methods We assessed lesional and nonlesional skin from 59 patients with moderate-to-severe AD treated with anti–IL-22 (fezakinumab) versus placebo (2:1) using transcriptomic and immunohistochemistry analyses. Results Greater reversal of the AD genomic profile was seen with fezakinumab versus placebo, namely 25.3% versus 10.5% at 4 weeks (P = 1.7 × 10−5) and 65.5% versus 13.9% at 12 weeks (P = 9.5 × 10−19), respectively. Because IL-22 blockade showed clinical efficacy only in patients with severe AD, we used baseline median IL-22 mRNA expression to stratify for high (n = 30) and low (n = 29) IL-22 expression groups. Much stronger mean transcriptomic improvements were seen with fezakinumab in the IL-22–high drug-treated group (82.8% and 139.4% at 4 and 12 weeks, respectively) than in the respective IL-22–high placebo-treated group (39.6% and 56.3% at 4 and 12 weeks) or the IL-22–low groups. Significant downregulations of multiple immune pathways, including TH1/CXCL9, TH2/CCL18/CCL22, TH17/CCL20/DEFB4A, and TH22/IL22/S100A's, were restricted to the IL-22–high drug group (P Conclusions This is the first report showing a profound effect of IL-22 blockade on multiple inflammatory pathways in AD. These data, supported by robust effects in patients with high IL-22 baseline expression, suggest a central role for IL-22 in AD, indicating the need for a precision medicine approach for improving therapeutic outcomes in patients with AD.

Background Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. Results At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. Limitations The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. Conclusion Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

Beyond classic “allergic”/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.

Background Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and non-lesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to non-lesional skin remains unclear. Methods We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 non-lesional AD biopsies, compared to 6 healthy control and 6 cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts. Results While greater T-cell infiltrates were observed in lesional vs. non-lesional AD, TCR repertoire diversity was similar in lesional and non-lesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with non-lesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and non-lesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-β genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g. IL-13, CCL17, IL23p19, CXCL10). Conclusion While AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and non-lesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T-cells well beyond clinically inflamed lesions. This article is protected by copyright. All rights reserved.

Acitretin has been associated with alopecia and hair shaft abnormalities such as hair kinking, hair curling, poliosis, and re-pigmentation of hair color. In the majority of patients, these side effects are dose-dependent, mild, and only temporary, with hair growth reoccurring after cessation of treatment. A 65-year-old male developed severe hair loss over his entire body seven weeks into treatment. He presented to us more than six months after discontinuation of acitretin without evidence of substantial hair regrowth. Here we report one of the rare cases of long-lasting alopecia after therapy with acitretin that we believe to be a case of generalized telogen effluvium.

Statins have immunomodulatory effects. Hence, they could be advantageous for different reasons. First, statins can serve as adjunct therapy in autoimmune diseases. Second, they may play a role in the prevention of accelerated atherosclerosis in the same population. In this review, we discuss the mechanisms of immune regulation by statins and review the literature for their benefit in many autoimmune diseases. In these studies, statins lead to an improvement in the disease activity scores in rheumatoid arthritis patients; a reduction in prothrombotic factors in anti-phospholipid syndrome patients; changes in vasculature, proteinuria, and cardiac events in systemic lupus erythematosus patients; changes in vasculature and proteinuria in patients with vasculitis; disease activity scores in ankylosing spondylitis; and finally vascular changes in patients with systemic sclerosis. Hence, these studies suggest that statins could be used as adjuncts to standard therapy due to their anti-inflammatory, immunomodulatory, and anti-thrombogenic effects. More evidence-based research is required to determine whether statin regimens will become the standard of care in patients with autoimmune diseases.

The aim of this study is to define the rheumatic manifestations of euthyroid patients with chronic lymphocytic thyroiditis (CLT) but without a well-defined connective tissue disease. Forty-six consecutive patients with anti-thyroid peroxidase (αTPO) and/or anti-thyroglobulin antibodies (αTG), and normal thyroid function in the absence of a well-defined connective tissue disease were included in a case-cohort study. Arthralgias were a presenting complaint in 98 % of patients. Fibromyalgia syndrome was found in 59 % of patients. Raynaud's phenomenon occurred in 28 % and sicca symptoms in 26 % of patients. Two patients had seronegative arthritis resembling rheumatoid arthritis. Arthritis was radiographically present in 88 %, affecting the spine in 45 % of patients. Thyroid-stimulating hormone (TSH) levels positively correlated with levels of αTPO, but not with erythrocyte sedimentation rate (ESR) or αTG levels. A positive ANA was found in 24 % of patients. One patient developed subclinical hypothyroidism during the study. Rheumatic manifestations frequently occur in patients with CLT in the absence of overt thyroid dysfunction and mimic the presentation of the well-defined connective tissue diseases.

The increased awareness of the role of humoral immunophysiology in antiphospholipid syndrome (APS) has aroused interest in B cells as therapeutic targets in this disease. This paper reviews the literature on B cell directed therapies in human and experimental APS. The clinical data is limited to B cell depletion with rituximab and comprises case reports and case series. Murine studies include use of modulators of B cell function such as belimumab and abatacept. In both human and murine studies, B cell directed therapies appeared to have clinical and serologic beneficial effects including a decrease in the antiphospholipid antibody titers after treatment. Randomized controlled clinical trials are needed to determine whether B cell depletors and/or B cell modulators can be effective agents for treating patients with APS.

Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.

Objective.In a cohort of systemic lupus erythematosus (SLE) patients with endstage renal failure, to evaluate whether continuing rheumatology followup visits and immunosuppressive therapy after starting renal replacement were associated with increased survival.Methods.We identified all SLE patients over 21 years old who started renal replacement therapy between 2005 and 2011 at an urban tertiary care center. Mortality data were obtained using in-hospital records and the US Social Security Death Index database.Results.We identified 80 SLE patients undergoing renal replacement therapy. Twenty-two patients (28%) were followed in rheumatology clinics frequently (2 or more visits per year) after starting renal replacement therapy, and 58 patients (72%) were followed infrequently (fewer than 2 visits per year). Survival rates were significantly higher in transplant patients compared with dialysis patients. Patients with SLE followed frequently after starting dialysis had significantly higher 4-year survival rates compared with patients followed infrequently after starting dialysis (log-rank p = 0.03). In the Cox proportional hazards model, treatment with prednisone alone or with no medication was associated with a hazard ratio (HR) of death = 6.1 (95% CI 1.1, 34; p = 0.04) and HR = 13 (95% CI 1.5, 106; p = 0.02), respectively, compared with patients treated with a combination of immunosuppressive therapy with or without prednisone, adjusted for age at SLE diagnosis, sex, transplant status, and the frequency of rheumatology visits after the development of endstage renal failure.Conclusion.Active disease in patients with SLE undergoing renal replacement therapy may be underrecognized and undertreated, leading to increased mortality.

Background Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated. Objective We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge. Methods Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber). Results Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, T H 1-subset, and T H 2-subset genes in nickel-related AD responses, with increased T H 17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD. Conclusions Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of T H 1 products, some increases in levels of T H 17 products, and inconsistent upregulation in levels of T H 2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased T H 2, T H 17, and negative regulator levels compared with those seen in non-AD skin.

Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed.We sought to define the cutaneous molecular and structural effects induced by petrolatum.Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only.Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human β-defensin 2 [DEFB4A]/FCH, 4.96; P.001 for all) and innate immune genes (IL6, IL8, and IL1B; P.01) were observed in petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects.Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.

Primary Sjogren's syndrome is an autoimmune disease wherein there is lymphocytic infiltration of salivary and lacrimal glands. This inflammation is thought to be caused by B-lymphocytes. The most common clinical feature of Sjogren's is dryness of the mouth and eyes, but rare complications can occur such as autoimmune cytopenias. Here we report two cases of immune mediated cytopenias that were diagnosed to be due to Sjogren's syndrome. In both cases, immune suppressive treatment was required.

Systemic Lupus Erythematosus (SLE) is a multi-systemic autoimmune disorder that can have severe and potentially life-threatening manifestations. One such manifestation is lupus nephritis. While survival rates have improved significantly, SLE, and in particular lupus nephritis, continues to be associated with significant morbidity and mortality. The incidence of SLE varies greatly among different populations. As a whole, rates are highest in non-Caucasians. Estimated incidence rates of SLE are similar in the US and in Europe where Caucasians have rates of 3.5-4 per 100,000 and those of African descent have significantly higher rates of 9.2-11.4 per 100,000.1,2 While the disease is present to a certain degree in all populations, SLE affects primarily women in their child-bearing years with a ratio of 9:1 compared to men.3,4 When men do present with SLE there is evidence that they have worse disease outcomes including increased mortality.5,6 Regardless of race or gender, mortality in SLE has improved significantly since the 1950’s, where the 5-year survival rate was approximately 50%.7 Currently, 10-year survival rates range between 85% and 95%.7 Despite improved overall survival, lupus nephritis (seen in upwards of 60% of all SLE patients) continues to significantly affect morbidity and mortality.8 While 5-year survival for those without nephritis is approximately 92%, those with this complication have a much lower rate of 82%.8 Both in the US and in Europe, non-Caucasians have increased rates of nephritis, where not only is the condition more prevalent in these groups, it also tends to be more severe.5,9 In the US, risk factors for progression to end-stage renal disease include: being African American, Hispanic, male, less than 24 years old and having high activity and chronicity on renal biopsy.10 Risk factors notwithstanding, it has been shown that patients that receive early treatment have better outcomes.11,12 However, even with early and aggressive treatment, one study has found no change in the incidence of end-stage renal disease from lupus nephritis.13 Therefore, it appears that while medications are usually effective in controlling renal inflammation, a substantial amount of patients fail treatment. In addition, conventional therapies are not target-specific and can lead to significant toxicity. Therefore, given that B cells play such an integral role in the pathogenesis of SLE and lupus nephritis, these cells are potential targets for more specific therapies.

Takotsubo cardiomyopathy is a syndrome characterized by transient apical ballooning or reversible midventricular systolic dysfunction. Most cases occur in postmenopausal women and are typically triggered by an acute medical illness or emotional or physical stress. Its presentation is highly suggestive of myocardial ischemia, but there is little or no evidence of epicardial coronary artery disease. To our knowledge there are only three reported cases in the literature of Takotsubo cardiomyopathy induced by opioid agonist withdrawal in adults; ours is the first reported case of iatrogenic methadone withdrawal leading to Takotsubo cardiomyopathy.

A 75-year-female with a history of Isoniazid (INH) therapy for latent tuberculosis, was admitted with a 4-week duration of dyspnea, cough, and pleuritic chest pain. She was treated with intravenous antibiotics for a diagnosis of pneumonia. Her stay was complicated by development of recurrent, exudative eosinophilic pleural effusions (EPEs). When symptoms continued to worsen and she developed joint pain and anasarca and did not respond to the antibiotics, a rheumatologic work-up was performed. She was found to have positive anti-double stranded-DNA antibodies and anti-histone antibodies; thus, a diagnosis of drug-induced lupus, secondary to INH, was made. INH was discontinued, and the patient was started on prednisone; within weeks her symptoms resolved. This case illustrates a unique side effect of INH that caused exudative EPEs and drug-induced lupus with positive anti-dsDNA.

Introduction We describe a case of non-small cell lung cancer that was found to stain positive for beta-human chorionic gonadotropin on immunohistochemistry. Only a few case reports have described lung cancers that secrete beta-human chorionic gonadotropin. Case presentation A 68-year-old Caucasian man presented with symptoms of weakness, fatigue and weight loss for the past two months. On examination, he was found to have generalized lymphadenopathy, and radiologic workup revealed numerous metastases in the lungs, liver and kidneys. Biopsy of the supraclavicular lymph node revealed metastatic large cell lung cancer with beta-human chorionic gonadotropin hormone positivity. The serum beta-human chorionic gonadotropin level was 11,286 mIU/ml (upper limit of normal, 0.5 mIU/ml in non-pregnant females). He was diagnosed with stage 4 lung non-small cell lung cancer. The patient refused chemotherapy. He was discharged home with hospice care. Conclusion The markedly elevated serum values of beta-human chorionic gonadotropin initially prompted the medical team to investigate germinal tumors. In the presence of a negative testicular ultrasound, workup was performed to find an extratesticular source of the tumor. Finally, the diagnosis was made with a tissue biopsy. This case illustrates that atypical markers can be seen in many cancers, emphasizing the role of immunohistochemistry and tissue biopsy in establishing the diagnosis.