A Review of Primary Immunodeficiency Diseases with Skin Manifestations

Introduction: Primary immunodeficiencies (PID) are rare heterogeneous disorders with defects in which one or more components of the immune system are malfunctioning. Clinical presentations of the patients according to type of immunodeficiency are variable. The majority of these patients are susceptible to infections depending on the type of disorder. In these patients, one of the most important and common symptoms is a skin manifestation that in many cases helps to diagnose the disease. Skin symptoms can include infectious-inflammatory-autoimmune-allergic manifestations and malignancies. In some cases, skin involvement can be the initial manifestation of immunodeficiency diseases, so understanding the relationship between the type of primary immunodeficiency and the type of skin involvement is very important in diagnosing the disease. The majorities of skin diseases are not pathogenomonic in primary immunodeficiencies and may be seen in other diseases with normal levels of immunity. However, there are numerous skin findings that are so characteristic of immunodeficiency diseases that it is necessary to evaluate the immune system. Conclusion: Skin is an organ that may be involved in many diseases, including primary immunodeficiency. Sometimes skin is the first organ involved in immune deficiencies. Therefore, recognizing skin manifestations in these patients is one of the most important factors in early diagnosis of these people.

Paraneoplastic Filiform Hyperkeratosis and Immunoglobulin-Associated Vasculitis in Myeloma Progression: A Case Report

Multiple myeloma is a lymphoproliferative disease, which rarely presents with skin involvement or associated symptoms. Better awareness of these dermatological presentations is required for early diagnosis and to guide the patient towards appropriate therapy. We report on a patient with diffuse filiform hyperkeratosis and immunoglobulin-associated vasculitis in a severe progression of a known myeloma.

What factors guide treatment selection in mycosis fungoides and Sezary syndrome?

Cutaneous T-cell lymphoma (CTCL) comprises a spectrum of T-cell lymphomas with primary skin involvement. Mycosis fungoides (MF) and Sezary syndrome (SS) are the common subtypes of CTCL in which patients present with widely diverse profiles of skin involvement and varying extents of extracutaneous disease. Patients with early-stage disease have an excellent prognosis and are managed primarily with skin-directed therapies; however, those with advanced-stage MF or SS often require multiple lines and recurrent courses of systemic therapies. Many options are available when considering systemic agents, and it is often challenging to know how to prioritize therapies to address a patient's objective disease and quality of life issues. Appreciating the disease heterogeneity and understanding the patient's overall disease profile (eg, skin, lymph nodes, blood, large cell transformation) serve as a useful framework in aligning therapies that can optimally treat active sites of disease. Tissue or blood biomarkers can be integrated into our process of prioritizing therapies and personalizing management in MF or SS. Multidisciplinary management and optimizing supportive care are additional key elements for a favorable outcome. Appropriate patients with high-risk disease should be considered for allogeneic hematopoietic stem cell transplant.

Hands and feet radiologic involvements in systemic sclerosis

Aim Systemic sclerosis (SSc) is a rare autoimmune disorder characterized by vascular and fibrosing involvement of the skin and internal organs. In this study we determined the prevalence and characteristics of radiological hands and feet involvements in Iranian SSc patients identified disease–phenotype associations. Methods 43 SSc patients (41 women and 2 men), with a median age of 44.79 years (ranges 26 to 70 years) and a mean disease duration of 11.78 years (ranges 2 to 28 years) were studied in this cross-sectional study. Results 42 patients had radiological changes both in hands and feet. Only one patient had changes just in hand. The most frequent changes that we found in hand was Juxta-articular Osteoporosis (93%), Acro-osteolysis (58.2%), Joint Space Narrowing (55.8%). The prevalence of joint space narrowing or acro-osteolysis were higher in subjects with active skin involvement (modified Rodnan skin score (mRSS)>14) (16/21 v 4/16 for patients with inactive skin involvement (mRSS<14); p = 0.002). The most frequent changes that we found in foot were Juxta-articular Osteoporosis (93%), Acro-osteolysis (46.5%), Joint Space Narrowing (58.1%), subluxation (44.2%). The presence of anti-ccp antibody was detected in 4 (9.3%), while positive rheumatoid factor was found in 13 (30.2%) of SSc patients. Conclusion This study corroborates that an arthropathy is common in SSc patients. The introduction of the specific radiological involvements of SSc needs to be confirmed by further studies. in order to define the appropriate prognosis and treatment of patients.

Can any breast skin thickening be staged as T4?

Data analysis showed that many diagnostic issues in breast cancer patients with skin involvement are not systematized. In some cases when the tumor is small and skin involvement symptoms are minimal ("local" skin edema), should this category of patients be considered as patients with non-inflammatory skin involvement breast cancer? Current research confirms the presence of skin involvement has much less prognostic value than, for example, tumor size or lymph node metastases, and the surgical term "unresectable" may not always be adequate. In addition, clinical data often do not correspond to pathological data, which also complicates the staging and leads to "overtreatment" of such patients. Thus, further research is needed to identify categories of breast cancer (patients with skin involvement similar in prognosis, as well as to individualize approaches to local and systemic treatment.

Bacterial Prophylaxis in Patients with Acute Gvhd; Who Is at Risk for Bloodstream Infections?

Consensus on the need for antibacterial prophylaxis in patients with acute graft-vs.-host disease (AGVHD) has not been established with practices varying across centers. The aim of this study was to determine the risk for bacterial bloodstream infections (BSI) from neutrophil engraftment through day 100 post-hematopoietic cell transplant (HCT) in patients with AGVHD and whether organ involvement and severity impact this risk. Methods: The cause-specific hazards for developing BSI after-engraftment by day 100 was compared between patients with and without grade II-IV AGVHD by treating AGVHD as a time-dependent variable. Results: A total of 4064 adult patients who underwent a matched related, matched unrelated, or mismatched unrelated T-cell replete, marrow or blood HCT for AML, ALL, or MDS from 2008-2012 within the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients, 62% of which had lower GI involvement and 70% had skin involvement. In multivariate analysis (MVA), the hazard ratio for BSI was 1.83 (95% CI: 1.53-2.18; p&lt;0.0001) in those with grade II-IV AGVHD vs. those with grade 0/I. Patients with grade III/IV AGVHD had the highest risk for BSI (HR 2.45; 95% CI 1.99-3.0; p &lt;0.0001) with a borderline risk for those with grade II (HR 1.35; 95% CI 1.03-1.77; p=0.0275). Patients with lower GI involvement had higher risk when compared to those with grade II-IV AGVHD without GI involvement (HR 1.54; 95% CI 1.17-2.02; p=0.0019) with risk being incrementally higher with each lower GI stage (1-4). Patients with isolated stage 3 skin AGVHD (n=214) did not have significantly higher risk for BSI (HR 1.25; 95% CI 0.82-1.91; p= 0.3); however, those with isolated stage 4 (n=27) had higher risk (HR 3.30; 95% CI 1.74-6.27; p=0.0003) when compared to those with grade 0/I AGVHD. In MVA, patients who developed a BSI between engraftment and day 100 post-transplant had worse survival (HR 1.64, 95% CI 1.43-1.87; p &lt;0.001) and higher non-relapse mortality (NRM), HR 2.22; 95% CI 1.91-2.59; p &lt;0.001). When evaluating type of infections: Gram negative bacteremia was seen in a higher proportion of patients (7%) with lower GI involvement vs. 4% in those without lower GI involvement and 4% in those with grade 0/1 AGVHD (p &lt;0.01). Staphylococcus aureus bacteremia was seen in a higher proportion of patients with grade 2-4 AGVHD with skin involvement (4%) vs. 2% in those without skin involvement and 1% in those with grade 0/1 AGVHD (p &lt;0.01). Conclusions: Patients with grade II-IV AGVHD are at higher risk for BSI compared to patients with grade I AGVHD or no AGVHD. Those with lower GI involvement or with stage 4 skin AGVHD are at highest risk. The development of BSI is associated with worse survival and higher NRM. Strategies for the lowering the risk for BSI in high risk patients are needed. Figure 1 Figure 1. Disclosures Gulbis: EUSA Pharma: Other: Advisory board participation. Kitko: Vanderbilt University Medical Center: Current Employment; Co-investigator on two NIH grants as part of the cGVHD consortium: Research Funding; Horizon: Membership on an entity's Board of Directors or advisory committees; PER: Other: PER - CME educational talks about GVHD. MacMillan: Equilium: Other: DSMB member; Incyte: Consultancy; Jazz Pharmaceuticals: Consultancy. Pidala: CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Regeneron: Consultancy; Pharmacyclics: Other: Clinical trial support, Research Funding; Incyte: Consultancy; Takeda: Other: Clinical trail support; Novartis: Other: Clinical trail support; BMS: Other: Clinical trial support, Research Funding; Johnson and Johnson: Other; Jannssen: Other: Clinical trial support; BMS: Other; AbbVie: Other. Riches: Jazz Pharmaceuticals: Other: Payment; BioIntelect: Membership on an entity's Board of Directors or advisory committees; ATARA Biotherapeutics: Other: Payment. Arora: Kadmom: Research Funding; Syndax: Research Funding; Pharmacyclics: Research Funding.