Diagnostic Criteria for a Curable Form of Chronic Rhinosinusitis: The Mucous Recirculation Syndrome

In clinical practice, nonallergic rhinosinusitis (rhinopathy) is a common diagnosis of exclusion. The mucous recirculation syndrome is one incompletely defined condition that masquerades as nonallergic rhinopathy. Mucous recirculation syndrome, a curable condition, should be differentiated from nonallergic rhinopathy. The underdiagnosis of this condition is due in part to a lack of diagnostic criteria. In this article, we review the medical literature to better characterize mucous recirculation syndrome and to establish diagnostic criteria for it.     

Be careful of the masquerades: differentiating secondary myelodysplasia from myelodysplastic syndromes in clinical practice

In patients suspected to have myelodysplastic syndrome (MDS), especially in those patients without cytogenetic abnormalities or blast excess, accurate morphologic review by an expert hematopathologist and meticulous exclusion of other secondary causes of myelodysplasia are vital to establish the diagnosis. Errors in diagnosis can lead to dangerous consequences such as the administration of hypomethylating agents, lenalidomide, or even the use of intensive chemotherapy or allogeneic hematopoietic cell transplantation in patients who do not have an underlying MDS or even a malignant hematopoietic process. Additionally, beyond the possible harm and lack of efficacy of such therapies if the diagnosis of MDS is erroneous, the secondary myelodysplasia and resultant cytopenias are not likely to resolve unless the underlying etiology is identified and addressed. Discriminating a malignant process such as MDS from non-malignant secondary myelodysplasia can be quite challenging, and community hematologists/oncologists should consider referral to specialized physicians (both clinical experts and experienced hematopathologists) if there is any doubt regarding the diagnosis. In this article, we present a representative case series of patients from our own practice who posed diagnostic dilemmas and propose a systematic approach for assessment for secondary causes of myelodysplasia.     

Non-alcoholic fatty liver disease. How and who to screen

Non-alcoholic fatty acid disease (NAFLD) can develop in the context of multiple processes but the main etiologic association is undoubtedly with insulin resistance syndrome. The present review aims to provide a systematic diagnostic approach that should include the following basic elements: a) a suspected diagnosis of NAFLD, including confirmation of abstinence from alcohol, exclusion of other potential causes of liver steatosis and diagnosis of potential associated diseases; b) diagnosis of insulin resistance; c) diagnosis of potential associated diseases; d) adequate evaluation of vascular risk; e) diagnosis of the type and localization of fat, and finally, f) evaluation of the severity of NAFLD, which can be performed through invasive and non-invasive techniques.     

The diagnosis of sarcoidosis

The diagnosis of sarcoidosis can never be assured: sarcoidosis is a diagnosis of exclusion and this cannot be accomplished with complete confidence. The diagnosis requires clinicoradiographic findings compatible with the diagnosis, histologic confirmation of granulomatous inflammation, exclusion of known causes of granulomatous disease, and evidence of disease in at least two organs. The end result of this diagnostic evaluation for sarcoidosis is neither a definitive diagnosis nor an exclusion of the diagnosis, but rather a statistical likelihood of the disease.     

The enigmas of the lupus anticoagulant: Mechanisms,diagnosis, and management

Lupus anticoagulant (LA) is a laboratory abnormality associated with the antiphospholipid syndrome. It is a paradoxical phenomenon in which one or more in vitro diagnostic clotting tests are prolonged and thus seem due to an anticoagulant, whereas the antiphospholipid syndrome is manifest clinically as inappropriate or excessive thrombosis. LA should be suspected when thrombosis, recurrent fetal loss, or a prolonged phospholipid (PL)-dependent clotting test is present without other identifiable causes. Despite the heterogeneity of LA antibodies, a consensus has evolved to identify the LA. Four conditions must be met for this laboratory diagnosis: 1) prolongation of a PL-based clotting test, 2) confirmation of an inhibitor-like pattern in the clotting test, 3) confirmation of PL dependence in coagulation tests, and 4) exclusion of a specific factor inhibitor. Even with an extensive armamentarium for LA diagnosis and treatment, it is still a formidable task.     

Thoraxschmerz in der Notaufnahme

Patients with chest pain are a common problem in private practice and emergency admissions in hospitals. The differential diagnosis of this common symptom encompasses a vast spectrum of various diseases with different needs for urgent therapy and immediate diagnosis. This overview summarizes the various aspects of the different origins, the basics of medical history and clinical examinations as well as the appropriate subsequent diagnostic assessment. Besides the most common and clinically important causes, such as acute coronary heart syndrome, other origins with a necessity for immediate diagnosis and therapy, such as pulmonary embolism and dissection of the aorta, have to be considered. However, after exclusion of these emergency situations with immediate therapeutic needs other differential diagnoses have to be considered. The spectrum ranges from functional and vertebral thoracic pain, reflux disease and other esophageal disorders to other rare causes such as infections and trauma. These other causes need an interdisciplinary assessment which should not end with a negative coronary angiogram and negative upper gastro-intestinal endoscopy. It is of crucial importance that the correct pathways for clinical diagnosis and therapy are already prepared in the emergency unit.     

POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management

DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. RISK-ADAPTED THERAPY: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti-VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.     

POEMS syndrome: update on diagnosis, risk-stratification, and management

DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS syndrome is made with 3 of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. RISK-ADAPTED THERAPY: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti-VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.     

Aseptic abscesses syndrome

Aseptic abscesses syndrome is a systemic disorder of unknown etiology involving polymorphonuclear neutrophil. Typical presentation of aseptic abscesses syndrome includes fever, abdominal pain and leukocytosis, and is characterized by the presence of intra-abdominal aseptic lesions consisting of neutrophils. The diagnosis relies on a combination of a typical clinical and radiological presentation, the pathological findings, and the exclusion of alternative diagnosis, especially infectious diseases. Antibiotics fail to achieve cure but there is a marked improvement with corticosteroids. Aseptic abscesses syndrome is either associated with another disease such as Crohn's disease or relapsing polychondritis, or is idiopathic. It is often a relapsing condition and the PET may be an interesting diagnostic tool in the setting of recurrent and febrile abdominal pain. An immunosuppressive agent is required in almost half of the patients and anti-TNFα drugs may be used. Aseptic abscesses syndrome shares some features with other disorders such as inflammatory bowel diseases or neutrophilic dermatoses which suggests a genetic susceptibility and a relationship with auto-inflammatory disorders. Further studies on the pathways involved in aseptic abscesses will help to improve diagnosis and treatment.     

Idiopathische Lungenfibrose

The diagnosis of idiopathic pulmonary fibrosis (IPF) is based on a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy or specific combinations of HRCT with histopathological patterns after exclusion of known causes of interstitial lung disease. The diagnostic work-up should also include initial lung function and the diagnosis of comorbidities. The interdisciplinary discussion of clinical, radiological and histological data is essential.     

Cholestasis of pregnancy

Cholestasis of pregnancy is the commonest liver disease unique to pregnancy and is characterized by pruritus in the mother in late pregnancy, without any skin rashes. This is accompanied by an elevation of the serum bile acids. Liver function test abnormalities may occur. Abdominal pain is not a feature and liver failure does not occur. The diagnosis is made by a suggestive history and exclusion of other causes by the history, serology and an upper abdominal ultrasound. All symptoms and signs should disappear within 4 weeks post-partum; prolonged post-partum courses should prompt a search for other causes, such as primary biliary cirrhosis. The syndrome is associated with a five-fold increased incidence of stillbirth, intra-partum foetal distress and pre-term labour. The reason is not clear and not predictable. The accepted management is induction or delivery at 38 weeks, which has led to a reduction in poor foetal outcome. Preliminary studies using ursodeoxycholic acid show symptomatic and biochemical improvement in most women treated. There is also a suggestion of an improved foetal outcome and treatment should be considered in women who present with the condition earlier in pregnancy.     

POEMS syndrome: failure of newly suggested diagnostic criteria to anticipate the development of the syndrome

POEMS syndrome is a unique clinical entity. Although it's a diagnosis of exclusion, it was previously described by the presence of several typical characteristics as paraproteinemia, polyneuropathy, organomegaly, endocrinopathy, and skin changes. Recently, new criteria were proposed, and the presence of two major and one minor criterion was claimed to suffice for a diagnosis. Both methods considered other important characteristics germane to the syndrome unessential for diagnosis. Retrospective evaluation of patients with lymphoproliferative disease was carried out to reveal the presence of the syndrome according to these different methods. Patients' clinical progression during follow-up will be used to validate the criteria's sensitivity and specificity. Six hundred twenty-nine consecutive files of patients with paraproteinemia who were followed-up at a tertiary medical center were reviewed. Of 12 patients who fulfilled the new criteria for diagnosis of POEMS, 3 remain stable during long-term follow-up and only 5 finally developed the full-blown syndrome. Four patients developed other diseases that accounted for their clinical findings. Patients presenting with neuronal vasculitic changes on biopsy, kappa light-chain monoclonal gammopathy, and cryoglobulinemia were unlikely to develop POEMS syndrome, even though they fulfilled the newly suggested criteria. Although they are not in the criteria, sclerotic bone lesions were found only in patients who eventually developed the full syndrome. The diagnosis of POEMS syndrome according to the newly suggested criteria should not be definitive in the presence of atypical clinical features of the syndrome.     

Allopurinol-induced severe hypersensitivity with acute renal failure

A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS). Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.     

Swallowing disorders: a challenge for the gastroenterologist

Alterations in the physiological mechanism of swallowing involve several anatomical structures performing complex and coordinated activities. These alterations can be secondary to various pathological conditions with highly varied causes. Consequently, the approach to patients with swallowing disorders represents a diagnostic challenge. The first difficulty arises in establishing a diagnosis of the syndrome, in which the presence of dysphagia is often the key symptom. The second difficulty lies in identifying the alteration: distinguishing between those affecting the oral and pharyngeal phases and those affecting the pharyngeal phase is clinically important since the etiology and diagnostic strategy will differ. Whenever possible, treatment should be etiological and should aim to restore the swallowing mechanism. Alternative routes for nutrition are sometimes required, either because etiological treatment is lacking or to avoid complications.     

Differential diagnosis of the patient with unexplained flushing/anaphylaxis.

In unusual cases of flushing and anaphylaxis, and after the elimination of the more obvious causes of anaphylaxis or those that may be evaluated by readily available techniques, it is possible to confront a limited and difficult differential diagnosis, which includes idiopathic flushing, anaphylaxis, and neoplastic syndromes associated with mastocytosis and carcinoid tumor. Interestingly, there are rather few features that distinguish one of these possibilities from another. However, the presence of allergic signs and symptoms tend to favor the diagnosis of recurrent idiopathic anaphylaxis; and right-sided valvular heart disease, the presence of excessive 5-HIAA in the urine, and a response to somatostatin favor the diagnosis of carcinoid syndrome. The distinguishing features of mastocytosis include the presence of characteristic skin lesions and diagnostic histopathologic findings on bone marrow biopsy. Counts of absolute mast cell numbers in the skin are less helpful. Following such guidelines, it is often possible to focus on the most likely diagnosis, be it idiopathic anaphylaxis, benign cutaneous flushing, mastocytosis, or carcinoid tumor.     

Pitfalls in the diagnosis of immune thrombocytopenic purpura in children: 4 case reports.

Acute idiopathic thrombocytopenic purpura is the most common cause of thrombocytopenia in childhood, and diagnosis of idiopathic thrombocytopenic purpura is made clinically based on the exclusion of other causes of thrombocytopenia. Patients with diverse causes of thrombocytopenia are sometimes erroneously diagnosed as having idiopathic thrombocytopenic purpura. However, for the prevention of misdiagnoses, careful inspection of peripheral blood smear is of utmost importance. This report presents 4 cases presumed as acute idiopathic thrombocytopenic purpura that were finally identified as pseudothrombocytopenia, inherited macrothrombocytopenia (MHY9 disorders) possibly Epstein syndrome, Bernard-Soulier syndrome, and drug-induced thrombocytopenia. They draw attention to the importance of platelet morphology to exclude inherited macrothrombocytopenia and history to exclude drug-induced thrombocytopenia. Better diagnostic approaches would be possible by the awareness of these relatively rare causes of isolated thrombocytopenia.     

Evaluation of pulmonary infiltrates in patients after stem cell transplantation

Hematopoietic stem cell transplantation is potentially curative therapy that has become the standard of care for many hematologic malignancies. Pulmonary complications occur in about 50% of stem cell transplant recipients and no other organ dysfunction has a higher mortality. Unfortunately the diagnosis of these infiltrates is hampered by the poor yield from routine studies and this patient population is rarely able to tolerate more risky procedures that will obtain tissue for microscopy and culture. A bronchoalveolar lavage (BAL) is usually insufficient to make a diagnosis of invasive fungal, significant bacterial, or pathogenic viral infections in patients that will still benefit from a change in therapy. In this review we discuss the infectious etiologies of pulmonary infiltrates post hematopoietic stem cell transplant, the non-infectious causes of infiltrates such as diffuse alveolar hemorrhage, engraftment syndrome, and idiopathic pneumonia syndrome, and the yield of newer diagnostic procedures ranging from peripheral blood galactomannan to cytomegalovirus antigenemia, and report on new technologies that promise more accurate and timely diagnoses of these infiltrates.     

Evaluation of pulmonary infiltrates in patients after stem cell transplantation

Hematopoietic stem cell transplantation is potentially curative therapy that has become the standard of care for many hematologic malignancies. Pulmonary complications occur in about 50% of stem cell transplant recipients and no other organ dysfunction has a higher mortality. Unfortunately the diagnosis of these infiltrates is hampered by the poor yield from routine studies and this patient population is rarely able to tolerate more risky procedures that will obtain tissue for microscopy and culture. A bronchoalveolar lavage (BAL) is usually insufficient to make a diagnosis of invasive fungal, significant bacterial, or pathogenic viral infections in patients that will still benefit from a change in therapy. In this review we discuss the infectious etiologies of pulmonary infiltrates post hematopoietic stem cell transplant, the non-infectious causes of infiltrates such as diffuse alveolar hemorrhage, engraftment syndrome, and idiopathic pneumonia syndrome, and the yield of newer diagnostic procedures ranging from peripheral blood galactomannan to cytomegalovirus antigenemia, and report on new technologies that promise more accurate and timely diagnoses of these infiltrates.     

POEMS syndrome: Update on diagnosis,risk‐stratification,and management

Disease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti‐VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 90:951–962, 2015. © 2015 Wiley Periodicals, Inc.     

The lung in systemic vasculitis

Pulmonary vasculitis is usually caused by one of three disorders: (1) Wegener's granulomatosis (WG); (2) Churg-Strauss syndrome (CSS), or allergic angiitis and granulomatosis; or (3) a nonspecific small vessel systemic necrotizing vasculitis (SNV), or microscopic polyarteritis. WG, the most common cause of lung vasculitis, has features of a granulomatous vasculitis of the upper airway and lung and widespread small vessel vasculitis involving the kidneys and other organs. The features of pulmonary WG overlap with those of malignancy and infectious granulomatous lung disease; accurate diagnosis generally requires open lung biopsy. CSS is defined by the triad of asthma, eosinophilia, and systemic vasculitis. Easily accessible tissues should be biopsied, but the clinical features are so distinctive that tissue biopsy is not invariably required for diagnosis. CSS must be differentiated from other diseases that cause pulmonary infiltrates with eosinophilia, including infections. Nonspecific SNV causes diffuse alveolar hemorrhage due to pulmonary capillaritis. Concomitant segmental necrotizing glomerulonephritis is almost always present. Diagnosis is made by renal biopsy, compatible extrarenal features, exclusion of nonimmune causes of lung hemorrhage, and exclusion of WG to the extent possible.