Mrinal M. Patnaik

Eosinophilia: secondary, clonal and idiopathic.

Blood eosinophilia signifies either a cytokine‐mediated reactive phenomenon (secondary) or an integral phenotype of an underlying haematological neoplasm (primary). Secondary eosinophilia is usually associated with parasitosis in Third World countries and allergic conditions in the West. Primary eosinophilia is operationally classified as being clonal or idiopathic, depending on the respective presence or absence of a molecular, cytogenetic or histological evidence for a myeloid malignancy. The current communication features a comprehensive clinical summary of both secondary and primary eosinophilic disorders with emphasis on recent developments in molecular pathogenesis and treatment.

Systemic mastocytosis: a concise clinical and laboratory review.

CONTEXT Systemic mastocytosis is characterized by abnormal growth and accumulation of neoplastic mast cells in various organs. The clinical presentation is varied and may include skin rash, symptoms related to release of mast cell mediators, and/or organopathy from involvement of bone, liver, spleen, bowel, or bone marrow. OBJECTIVE To concisely review pathogenesis, disease classification, clinical features, diagnosis, and treatment of mast cell disorders. DATA SOURCES Pertinent literature emerging during the last 20 years in the field of mast cell disorders. CONCLUSIONS The cornerstone of diagnosis is careful bone marrow histologic examination with appropriate immunohistochemical studies. Ancillary tests such as mast cell immunophenotyping, cytogenetic/molecular studies, and serum tryptase levels assist in confirming the diagnosis. Patients with cutaneous disease or with low systemic mast cell burden are generally managed symptomatically. In the patients requiring mast cell cytoreductive therapy, treatment decisions are increasingly being guided by results of molecular studies. Most patients carry the kit D816V mutation and are predicted to be resistant to imatinib mesylate (Gleevec) therapy. In contrast, patients carrying the FIP1L1-PDGFRA mutation achieve complete responses with low-dose imatinib therapy. Other therapeutic options include use of interferon-alpha, chemotherapy (2-chlorodeoxyadenosine), or novel small molecule tyrosine kinase inhibitors currently in clinical trials.

Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders.

Kit a type III receptor tyrosine kinase, along with its ligand the stem cell factor, play a critical role in normal cell growth, differentiation, development and survival. Ligand independent activation of kit (dysregulated kit function) has been found to be an important component of oncogenesis in a large number of neoplastic disorders such as systemic mastocytosis, gastro intestinal stromal tumors, germ cell tumors, acute myelogenous leukemia with the disruption of the core binding factor, amongst others. The identification of small molecule inhibitors with activity against Kit, has offered a wider and more effective range of therapeutic options in the treatment of these neoplastic processes. Novel tyrosine kinase inhibitors such as imatinib, nilotinib and dasatinib, have been found to be effective in the management of various subtypes of systemic mastocytosis and gastrointestinal stromal tumors. Non-tyrosine kinase inhibitors like rapamycin, 17-AAG and IMD- 0354 have been added to the therapeutic armamentarium, with the hope that combination therapy might have a synergistic effect, or prevent/delay the development of drug resistance.

Pregnancy and thrombophilia

The physiological changes that occur during pregnancy create a hypercoagulable milieu. This hypercoagulable state is thought to be protective, especially at the time of labor, preventing excessive hemorrhage. The presence of hereditary or acquired causes of thrombophilia during pregnancy tilts the balance in favor of unwanted venous thromboembolism and adverse pregnancy outcomes due to vascular uteroplacental insufficiency. These adverse pregnancy outcomes include recurrent pregnancy losses, intrauterine fetal death, intrauterine growth retardation, preeclampsia and placental abruption. Much of the current data with regards to the association of the different thrombophilias and pregnancy-related complications are based on retrospectively designed studies. This lack of randomization, in-homogeneity of patient populations, varying case definitions, selection biases and inadequately matched control populations, have given rise to conflicting data with regard to screening for, and treatment of, pregnant women with suspected thrombophilias. The limited data that we have support the use of anticoagulant drugs for the prevention of pregnancy-related complications in the setting of thrombophilia. Heparin and low-molecular-weight heparins are the anticoagulant drugs of choice as they do not cross the placental barrier and, hence, do not cause fetal anticoagulation or teratogenicity. Warfarin can be used from the 12th week of gestation onwards but is preferably reserved for the postpartum period.

Diagnosis-Addison's disease secondary to tuberculosis of the adrenal glands

A diagnosis of Addison’s disease secondary to tuberculosis of the adrenal glands was made for the case presented in the December 2007 Aperture.1 The computed tomography (CT) scan in figure 1 ▶ demonstrates the presence of free fluid in the patient’s abdomen and bilateral cystic adrenal hyperplasia. The patient was started on four-drug anti-tuberculosis therapy (isoniazid, rifampin, pyrazinamide and ethambutol) along with hydrocortisone supplementation. Fludrocortisone was added to augment his blood pressure response. Over the next few weeks he showed a marked improvement in constitutional symptoms. The free fluid in the abdomen resolved, and he is currently on his eighth month of anti-tuberculosis drug therapy, along with continued steroid supplementation. Figure 1. CT scan indicating bilateral cystic adrenal hyperplasia and free fluid in the abdomen (arrow points to the very fine, hypodense region between the liver margin and the anterior abdominal wall). In 1855, Thomas Addison described autopsy findings of six patients with adrenal tuberculosis, which continues to be one of the most common causes of adrenal insufficiency in the developing world. In a recent study Guo et al,2 compared the contrast enhanced CT scan features of the adrenal glands in 42 patients with adrenal tuberculosis. Of these patients, 91% (38) had bilaterally enlarged adrenals and 51% (21) had enlarged glands with preservation of the contours.2 Other important, although less common causes of adrenal insufficiency that need to be considered in the clinical differential diagnosis include histoplasmosis, blastocmycosis, adrenal metastases, primary adrenal tumors and opportunistic infections related to HIV/AIDS.3

The Nepalese shepherd

Neurocysticercosis is one of the most common causes of seizures in the developing world. Due to the high volumes of immigration from South America and Asia, American physicians are increasingly encountering this condition. This case report attempts to present a brief overview of some of the difficulties associated with the treatment of patients with a high disease burden.

Pulmonary Nodules as an Extra-Intestinal Manifestation of Inflammatory Bowel Disease: A Case Series and Review of the Literature

Inflammatory bowel disease (IBD) exhibits a wide spectrum of pulmonary manifestations [1]. Pulmonary nodules, however, are an uncommon extra-intestinal manifestation (EIM) of IBD with only a few cases documented in the literature (Table 1). A review of the case reports reveal that the pulmonary nodules linked to IBD exhibit a variety of histological patterns. The pulmonary nodules and respiratory symptoms relating to the lung pathology respond favorably to systemic or oral corticosteroid therapy and all patients show resolution or substantial improvement of pulmonary nodules on follow-up radiographs (Table 1). We present a case series of three patients who presented with pulmonary nodules as an EIM of IBD. The English-language literature is reviewed and we will highlight the clinical as well as histological importance of pulmonary nodules in IBD.

Inclusion Bodies in Tick-Borne Diseases Diagnosed in Patients from Northern Wisconsin

Clinical Vignette Case 1 A 65-year-old man from northern Wisconsin, presented to the clinic with complaints of fever, chills, myalgias and severe fatigue. He lived on a farm and frequently visited the woods for hiking. On examination he was found to be febrile without hepatosplenomegaly or lymphadenopathy. His hemoglobin was 8 g/dL, white count was 2.8 with 1100 neutrophils, and the platelet count was 55,000/mm3. A peripheral smear was ordered.

Cystic Adrenal Hyperplasia – Diagnosis?

A 20-year-old male from rural India was brought to the hospital with complaints of persistent low-grade fevers, night sweats, weight loss, abdominal distention, multiple episodes of pre-syncope and a generalized failure to thrive. He was found to be hypotensive and had increased pigmentation of the skin (especially the palms and the oral mucosa). He had free fluid in the abdomen without organomegaly, lumps or masses. He had normal external genitalia and secondary sexual characteristics. His chest x-ray was normal. His laboratory work-up revealed an ESR of 90 mm and a random serum cortisol of <4 mg/dl. A computed tomography (CT) scan of the abdomen and pelvis showed the presence of bilateral cystic adrenal hyperplasia with preserved contours, and evidence of free fluid in the abdomen. There was no abdominal, retroperitoneal lymphadenopathy or thickening of the ileo-caecal region. An abdominal paracentesis revealed the fluid to be exudative with a negative gram stain and AFB stain. Of note, the ascitic fluid ADA (adenosine deaminase level) was elevated at 75 U/ml. He did not have any electrolyte abnormalities and his HIV ELISA was negative. The CT scan of his abdomen is shown in figure 1 ▶. What is your diagnosis? Figure 1. CT scan showing bilateral cystic adrenal hyperplasia.