Masashi Ohe

Lack of linkage between atopy and locus 11q13

Atopy as defined in terms of IgE responsiveness was reported to be controlled by a single gene in British families, and this concept was further supported by a significant linkage between atopy and restriction fragment length polymorphism (RFLP) detected by a DNA probe specific to chromosome 11q13. To confirm this observation in a Japanese population, segregation and linkage analyses were done in four large families. Although segregation patterns of atopy were in agreement with the pattern of autosomal dominant inheritance, there was no significant linkage between atopy and locus 11q13. Alterations in the definitions of atopy did not affect the results. These findings suggested the presence of heterogeneity in genetic elements of atopy, even though atopy may be determined mainly by a single dominant gene.

Pulmonary dysanapsis, methacholine airway responsiveness and sensitization to airborne antigen.

Abstract Whether the disproportional growth of airways relative to lung parenchyma (dysanapsis) has any relationship to the development of non‐specific bronchial hyperresponsiveness and atopy was investigated in 45 family members of the patients with atopic asthma. As indices of pulmonary dysanapsis, forced expiratory flow25‐75/forced vital capacity (FEF25‐75/FVC) and the tracheal cross sectional area divided by the forced expiratory volume (X‐SA/FVC) were examined. As an index of non‐specific airway responsiveness, the cumulative dose of inhaled methacholine needed to induce 35% reduction of respiratory conductance (PD35) was determined by continuous respiratory resistance measurement. For examination of atopy, skin prick tests were conducted, and total serum IgE and IgE specific to common inhaled antigens were measured. FEF25‐75/FVC showed no significant correlation to FVC but showed a significant correlation to log (PD35). When the analysis was done in the subjects whose FEVI/FVC was more than 0.8, FEF25‐75/FVC showed a significant negative correlation to FVC but lost its correlation to log(PD35). X‐SA/FVC showed a significant negative correlation to FVC but had no significant correlation to log(PD35). These relations were conserved when the analysis was done in subjects without airway obstruction. In addition, FEV1/FVC had a significant correlation to log(PD35) and FEF25‐75/FVC. However, subjects who had a positive IgE(MAST) had a significantly smaller X‐SA/FVC than those with a negative IgE(MAST) (0.60 ± 0.14[SD] and 0.72 ± 0.18, respectively, P<0.02). These results suggest that although pulmonary dysanapsis does not have a significant relation to airway responsiveness to inhaled methacholine, it may be associated with sensitization to airborne antigens.

Successful additional clarithromycin and tacrolimus treatment for hypereosinophilia associated with eosinophilic granulomatosis with polyangiitis

A 41-year-old man suffering from eosinophilic granulomatosis with polyangiitis (EPGA), diagnosed at another clinic on the basis of American College of Rheumatology Criteria, with a history of bronchial asthma, eosinophilia, mononeuritis multiplex, and non-fixed pulmonary infiltrates, was admitted to our department for further treatment. The patient complained of chest pain that started recently. An echocardiogram identified myocardial thickening and decreased wall motion, based on which the patient was diagnosed as having EPGA with myocarditis. The patient was successfully treated using glucocorticoids, such as methyl prednisolone (PSL) and PSL in combination with cyclophosphamide (CPM). However, CPM administration was discontinued afterwards because of the risk of bone marrow toxicity, the increased eosinophilic count (EOC) that we considered as an index of disease activity. Subsequently, the patient received additional clarithromycin (CAM) and tacrolimus (TAC) treatment considering their immunomodulatory effects. As a result, the EOC decreased and the PSL dosage could be reduced. This case shows that additional CAM and TAC treatment may be beneficial in some cases of EPGA.

Successful treatment of primary immune thrombocytopenia accompanied by diabetes mellitus treated using clarithromycin followed by prednisolone

Macrolides have immunomodulatory effects including anti-inflammatory effects as well as antibacterial activity. In consideration of these immunomodulatory effects, we report a patient with primary immune thrombocytopenia (ITP) treated using clarithromycin (CAM), a macrolide, followed by prednisolone (PSL). A 78-year-old man with thrombocytopenia was admitted to our hospital for further examination. Initial laboratory data showed reduced platelet counts (1.7 × 104/μL). Finally, we diagnosed the patient as having primary ITP. Because the patient was suffering from diabetes mellitus (DM), he was treated with CAM as an alternative to PSL. The platelet count increased to 6.1 × 104/μL. The CAM treatment was terminated owing to gradual nausea and palpitation. During the CAM treatment, the DM was under control. We reinitiated treatment for ITP. The patient was successfully treated using PSL without severe hyperglycemia. This case shows that CAM treatment may represent a useful option for ITP patients who cannot receive PSL due to DM.

A case of Waldenström's macroglobulinemia treated using clarithromycin and prednisolone

We report a case of Waldenströms macroglobulinemia (WM) treated using clarithromycin (CAM) and prednisolone (PSL). An 84-year-old woman was admitted to our hospital for bleeding after a tooth extraction and hematuria. Computed tomography showed multiple ill-defined nodules in the omentum (omental cake). Although the cause of the omental cake remained unclear, the patient was diagnosed with WM, based on the detection of M-protein of immunoglobulin (Ig) M in serum and lymphoplasmacytes in bone marrow. The bleeding tendency in the patient may have been due to acquired hemophilia and/or hyper IgM-induced platelet dysfunction. The patient was treated using CAM (800 mg/day) and PSL (10 mg/day). As a result, IgM levels gradually decreased. Because the omental cake contracted along with improvement in IgM, it was thought to be lymphoplasmacytic lymphoma-like lymphoma. This case shows that treatment using CAM and PSL may be effective in some cases of WM.

Multiple cavities with halo sign in a case of invasive pulmonary aspergillosis during therapy for drug-induced hypersensitivity syndrome

A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine. Human herpes virus 6 (HHV-6) variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA), and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patients general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients.

Successful treatment of three patients with organizing pneumonia associated with rheumatoid arthritis using clarithromycin and prednisolone

Macrolides have anti-inflammatory effects and have been used to treat diffuse panbronchiolitis, bronchiectasis, and cystic fibrosis. Lately, several cases of cryptogenic organizing pneumonia (COP) and radiotherapy-related organizing pneumonia (OP) that were successfully treated with macrolides considering their anti-inflammatory effects were reported. We report three cases of OP associated with rheumatoid arthritis (RA) successfully treated with clarithromycin (CAM) and prednisolone (PSL). Case 1: A 70-year-old woman suffering from RA was admitted with cough and severe dyspnea. She was diagnosed with OP associated with RA on the basis of computed tomography (CT) findings and transbronchial lung biopsy results. She was successfully treated with PSL and cyclosporine A. At the exacerbation of OP, she was successfully treated with CAM and PSL. Case 2: A 74-year-old man suffering from COP visited our department with arthralgia and articular swellings. He was diagnosed with RA, which was thought to be associated with OP. He was successfully treated with CAM and PSL. Case 3: A 54-year-old man suffering from RA presented with an exacerbation of arthralgia and articular swellings and cough. He was diagnosed with OP associated with RA on the basis of CT findings. He was successfully treated with CAM and PSL. The present cases suggest that CAM and PSL treatment may be effective in some cases of OP associated with RA.

A case of adult-onset Still's disease accompanied by pseudo-gray platelet syndrome

2000. 5. Pham A, Wang J. Bernard-Soulier syndrome: an inherited platelet disorder. Arch Pathol Lab Med 2007;131:1834-6. 6. Young G, Luban N, White JG. Giant platelet disorders in African-American children misdiagnosed as idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol 1999;21:231-6. 7. Sugi T, Makino T. Factor XII, kininogen and plasma prekallikrein in abnormal pregnancies. Curr Drug Targets 2005;6:551-7. 8. George JN, Caen JP, Nurden AT. Glanzmanns thrombasthenia: the spectrum of clinical disease. Blood 1990;75:1383-95. 9. Abolghasemi H, Shahverdi E. Umbilical bleeding: a presenting feature for congenital afibrinogenemia. Blood Coagul Fibrinolysis 2015;26:834-5. 10. Toogeh G, Keyhani M, Sharifian R, Safaee R, Emami A, Dalili H. A study of Bernard-Soulier syndrome in Tehran, Iran. Arch Iran Med 2010;13:549-51. 11. Dasanu CA, Alexandrescu DT. A case of prekallikrein deficiency resulting in severe recurrent mucosal hemorrhage. AM J Med Sci 2009;338:429-30. 12. Schmaier AH, McCrae KR. The plasma kallikrein-kinin system: its evolution from contact activation. J Thromb Haemost 2007; 5:2323-9. 13. Sollo DG, Saleem A. Prekallikrein (Fletcher factor) deficiency. Ann Clin Lab Sci 1985;15:279-85. 14. Saito H, Goodnough LT, Soria J, Soria C, Aznar J, España F. Heterogeneity of human prekallikrein deficiency (Fletcher trait): evidence that five of 18 cases are positive for cross-reacting material. N Engl J Med 1981;305:910-4. 15. François D, Trigui N, Leterreux G, et al. Severe prekallikrein deficiencies due to homozygous C529Y mutations. Blood Coagul Fibrinolysis 2007;18:283-6.