An Unusual Case of A Blue Finger

Introduction:Acute discoloration and paresthesia of a distal extremity is concerning for an ischemic event or a manifestation of underlying systemic disease. Achenbach syndrome is an infrequent, but benign etiology of an acute blue finger that needs to be recognized clinically. We present a case to increase awareness. Case:A 57-year-old Caucasian female presented to rheumatology clinic for bruising digits.” She described four episodes of spontaneous segmental, blue discoloration of varying digits over the past two years. Each episode was isolated to a single digit and preceded by 10-15 minutes of throbbing with the digit then turning white and numb. These prodromes were followed by a feeling of “blood vessel popping” with subsequent bruising and mild swelling. Resolution of discoloration ranged from several hours to several days. There was no association with exposure to cold temperatures and warming the fingers would not alleviate the symptoms, nor abort the course. Past medical history includes Raynaud’s disease diagnosed in her twenties. Her current symptoms feel distinctly different from usual Raynaud’s episodes. She is a non-smoker and takes no medications. Family history is non-contributory. Physical exam was unremarkable at presentation and follow up. Photos from the recent episode were available, revealing blue discoloration involving the volar surface of the right 3rd digit at the PIP extending 1cm on either side of the joint with mild swelling, sparing of the distal phalange and no abnormalities of the surrounding digits. Work-up for Raynaud’s included anti-nuclear antibodies and its sub-serologies, anti-phospholipid serologies, complements, complete blood count and complete metabolic panel. These studies were unremarkable and no autoimmune process was identified. The patient also underwent MRA of the right upper extremity, which was non-revealing. Based on the clinical presentation, a diagnosis of Achenbach syndrome was made and the patient was reassured. Discussion:Achenbach syndrome is a benign, self-limiting cause of spontaneous blue finger discoloration that is commonly misdiagnosed as vascular problems, including Raynaud’s. Unlike Achenbach syndrome, Raynaud’s episodes may involve multiple fingers simultaneously, is temperature related and warrants further work-up. In contrast, case studies and case series of Achenbach syndrome suggest futility of angiography and extensive rheumatologic work-up and have not demonstrated any significant disease associations over time. Despite the concerns raised by acuity and appearance, knowledge of Achenbach syndrome along with careful history taking will direct the physician to the correct diagnosis and avoid unnecessary, costly testing

The Role of Human Mast Cell-Derived Cytokines in Eosinophil Biology

Eosinophil-mediated diseases, such as allergic asthma, eosinophilic fasciitis, and certain hypersensitivity pulmonary disorders, are characterized by eosinophil infiltration and tissue injury. Mast cells and T cells often colocalize to these areas. Recent data suggest that mast cells can contribute to eosinophil-mediated inflammatory responses. Activation of mast cells can occur by antigen and immunoglobulin E (IgE) via the high-affinity receptor (FcεRI) for IgE. The liberation of proteases, leukotrienes, lipid mediators, and histamine can contribute to tissue inflammation and allow recruitment of eosinophils to tissue. In addition, the synthesis and expression of a plethora of cytokines and chemokines (such as granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-1 [IL-1], IL-3, IL-5, tumor necrosis factor-α [TNF-α], and the chemokines IL-8, regulated upon activation normal T cell expressed and secreted [RANTES], monocyte chemotactic protein-1 [MCP-1], and eotaxin) by mast cells can influence eosinophil biology. Stem cell factor (SCF)-c-kit, cytokine-cytokine receptor, and chemokine-chemokine receptor (CCR3) interactions leading to nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) expression, and other signaling pathways can modulate eosinophil function. Eosinophil hematopoiesis, activation, survival, and elaboration of mediators can all be regulated thus by mast cells in tissue. Moreover, because eosinophils can secrete SCF, eosinophils can regulate mast cell function in a paracrine manner. This two-way interaction between eosinophils and mast cells can pave the way for chronic inflammatory responses in a variety of human diseases. This review summarizes this pivotal interaction between human mast cells and eosinophils

Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial.

OBJECTIVE: To determine the efficacy of anakinra (recombinant interleukin-1 receptor antagonist) in improving 28-day survival in sepsis patients with features of macrophage activation syndrome (MAS). Despite equivocal results in sepsis trials, anakinra is effective in treating MAS, a similar entity with fever, disseminated intravascular coagulation (DIC), hepatobiliary dysfunction (HBD), cytopenias, and hyperferritinemia. Hence, sepsis patients with MAS features may benefit from IL-1 receptor blockade. DESIGN: Re-analysis of de-identified data from the phase III randomized interleukin-1 receptor antagonist trial in severe sepsis (Opal, et. al. Crit Care Med. 1997 Jul;25(7):1115–24). SETTING: Multi-center study recruiting through 91 centers from 11 countries in Europe and North America. PARTICIPANTS: Sepsis patients with MODS and/or shock (original study) were re-grouped based on presence or absence of concurrent HBD and DIC as features of MAS (HBD/DIC group). The “non-HBD/DIC” group included patients with only HBD, only DIC or neither. INTERVENTION: Treatment with anakinra or placebo. MAIN OUTCOME(S) AND MEASURE(S): 28-day mortality. STATISTICAL ANALYSIS: descriptive statistics, chi-square, ANOVA, logistic and Cox regression. RESULTS: Data were available for 763 adults from the original study cohort, randomized to receive either anakinra or placebo. Concurrent HBD/DIC was noted in 43 patients (5.6% of total, ages 18–75; 47% women). The 28-day survival was similar in both anakinra and placebo-treated non-HBD/DIC patients (71.4% vs. 70.8%, p=.88). Treatment with anakinra was associated with significant improvement in the 28-day survival rate in HBD/DIC patients (65.4% anakinra vs. 35.3% placebo), with HR for death 0.28 (0.11–0.71, p = 0.0071) for the treatment group in Cox regression. CONCLUSIONS AND RELEVANCE: In this subgroup analysis, IL-1 receptor blockade was associated with significant improvement in survival of patients with sepsis and concurrent HBD/DIC. A prospective randomized trial using features of MAS for mortality risk stratification should be undertaken to confirm the role of IL-1 blockage

Sepsis with liver dysfunction and coagulopathy predicts an inflammatory pattern of macrophage activation

BackgroundInterleukin-1 receptor antagonists can reduce mortality in septic shock patients with hepatobiliary dysfunction and disseminated intravascular coagulation (HBD + DIC), an organ failure pattern with inflammatory features consistent with macrophage activation. Identification of clinical phenotypes in sepsis may allow for improved care. We aim to describe the occurrence of HBD + DIC in a contemporary cohort of patients with sepsis and determine the association of this phenotype with known macrophage activation syndrome (MAS) biomarkers and mortality. We performed a retrospective nested case-control study in adult septic shock patients with concurrent HBD + DIC and an equal number of age-matched controls, with comparative analyses of all-cause mortality and circulating biomarkers between the groups. Multiple logistic regression explored the effect of HBD + DIC on mortality and the discriminatory power of the measured biomarkers for HBD + DIC and mortality.ResultsSix percent of septic shock patients (n = 82/1341) had HBD + DIC, which was an independent risk factor for 90-day mortality (OR = 3.1, 95% CI 1.4-7.5, p = 0.008). Relative to sepsis controls, the HBD + DIC cohort had increased levels of 21 of the 26 biomarkers related to macrophage activation (p < 0.05). This panel was predictive of both HBD + DIC (sensitivity = 82%, specificity = 84%) and mortality (sensitivity = 92%, specificity = 90%).ConclusionThe HBD + DIC phenotype identified patients with high mortality and a molecular signature resembling that of MAS. These observations suggest trials of MAS-directed therapies are warranted

Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis A Multinational, Multicenter Study of 362 Patients

Objective. To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA)