A 49-year-old man presented a progressive swelling and induration of the skin resulting in flexion contracture. He had a history of two tick bites at the age of 17 and 47 years. Serum anti-Borrelia-burgdorferi antibody was positive; isolation of B. burgdorferi from the skin lesion was unsuccessful. He had eosinophilia (white blood cells 8,300/μl, 33% eosinophils) and hypergammaglobulinemia. The diagnosis of Shulman syndrome (eosinophilic fasciitis) from clinical and histological findings was established. A part of the flagellin gene of B. burgdorferi was detected in a skin biopsy sample by using the polymerase chain reaction method. To the best of our knowledge, this is the first report of detection of B.-burgdorferi-specific DNA from a skin sample of Shulman syndrome.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is considered to belong to peripheral T-cell lymphoma. Its prognosis is grave and effective treatments have not been established. Recently, we gave oral cyclosporin A (CsA) to a patient with IBL-like T-cell lymphoma, and succeeded in achieving dramatic remission. In this case, serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF alpha) were elevated and decreased or returned to normal after achieving remission. Since CsA is a potent suppressor of the immune system and most notably T-cells, the immunosuppression of T-cell function might have played an important role in achieving remission in this case, although the precise mechanism still remains to be elucidated. The present case indicates that administration of CsA may be a very effective and safe selection of therapy for IBL-like T-cell lymphoma, as well as analogous disorders such as IBL and angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), thereby will contribute to improving the prognosis of patients with these diseases.

Omental milky spots are especially large and numerous in New Zealand Black (NZB) mice, which are known to develop spontaneous autoimmune diseases. We investigated omental milky spots in NZB mice by light and electron microscopy. The milky spots were composed of abundant lymphocytes/plasma cells with macrophages, neutrophils, eosinophils, megakaryocytes, and various stromal cells. In addition, clustered neutrophils in various maturation stages with occasional mitotic figures were frequently present in the milky spots: apparent neutrophilic myelopoiesis was present. The presence of megakaryocytes was sporadic. Considering the giant size of megakaryocytes, their direct migration into the milky spots from the bone marrow or spleen seems improbable. Thus, the presence of megakaryocytes was interpreted as probable megakaryopoiesis. Erythroblasts were not contained in the milky spots. These findings seem to indicate that the milky spots in NZB mice represent a special type of lymphoid tissue with active neutrophilic myelopoiesis and probable megakaryopoiesis. Reticulum cells in the milky spots in NZB mice had well-developed dense bodies consisting of clustered parallel tubules that showed a hexagonal array. However, the biological significance of these cells remains unknown.

IntroductionSarcoidosis is recognized as a multiorgan disorder characterized by the presence of non-caseating granulomas in the involved tissues. It has been suggested that sarcoidosis might be due to the exposure to infectious or non-infectious agents in genetically susceptible individuals. In particular, Propionibacterium acnes and Mycobacterium tuberculosis have been considered causative microorganisms. We report a case of P. acnes-associated sarcoidosis in which a drastic improvement was achieved with clarithromycin administration. A possible mechanism of clarithromycin action is discussed.Case presentationA 78-year-old Japanese-Mongoloid woman with P. acnes-associated sarcoidosis presented with a persisting fever, joint pains and generalized lymph node swelling. The diagnosis of sarcoidosis was confirmed by pathological and immunohistochemical studies of a biopsied lymph node. In this case, an oral administration of clarithromycin was applied. Soon after the initiation of this treatment her symptoms as well as lymph node swelling disappeared. The clarithromycin treatment was discontinued 3.5 months after its initiation. She is currently in good condition. The pathological analysis of her lymph node, which was obtained during the clarithromycin treatment, suggested an apoptosis-inducing effect of clarithromycin on the sarcoid granulomas.ConclusionsClarithromycin was found to be effective for treating sarcoidosis and seems to have important pharmacological effects such as immunosuppression, immunomodulation and induction of apoptosis in addition to its antimicrobial role. In this case, apoptosis in the sarcoid granulomas induced by clarithromycin administration might have resulted in satisfactory improvement.

A patient with M-proteinemia (IgM, kappa type), lymphocytosis, anemia, and massive splenomegaly, was diagnosed as having Waldenström's macroglobulinemia (WM). Since this case was refractory to chemotherapy, splenic irradiation was performed, which effectively reduced the serum IgM level, spleen size, and lymphocyte counts; however, its effect was transient. Splenectomy was then carried out. The spleen contained abundant IgM-producing lymphocytes, and after splenectomy, the serum IgM values decreased and the peripheral blood counts returned to near normal. The transient increases of serum IgM occurred during two infectious episodes postoperatively. The patient has now been in a satisfactory remission for six years after splenectomy. The removal of an IgM-producing/secreting site and release from hypersplenism may be the major mechanisms involved in achieving the durable remission after splenectomy. In individual cases of WM with massive splenomegaly, we recommend splenectomy as part of the management of this disorder.

Patients with rheumatoid arthritis (RA) are known to develop lymphoproliferative disorders (LPDs) during the course of illness, particularly in cases treated with methotrexate (MTX) for long periods. We describe a case of MTX-related Epstein-Barr-virus-(EBV-) associated LPD resembling Hodgkin's lymphoma (HL), in which a dramatic complete remission was achieved after withdrawal of MTX coupled with clarithromycin (CAM) administration. Withdrawal of MTX coupled with CAM administration seemed to be effective for treating MTX-related EBV-associated LPDs. In particular, an immunomodulative effect of CAM might have been involved in achieving complete remission.

Clarithromycin (CAM), a semisynthetic macrolide antibiotic, is a widely used antibacterial drug. Recently, the efficacy of CAM as an add-on drug for treating multiple myeloma (MM) has been noted. Its effect on treating MM has been confirmed in combination chemotherapies that include CAM. However, a single treatment of CAM has no efficacy for treating MM. Many myeloma growth factors (MGFs) including interleukin (IL)-6 are known to be closely involved in the development of MM. CAM has been shown to suppress many MGFs, particularly IL-6. The possible mechanisms of action of CAM in treating MM have been suggested to include its immunomodulatory effect, autophagy inhibition, reversibility of drug resistance, steroid-sparing/enhancing effect and suppression of MGFs. In addition, MM is characterised by uncontrolled cell growth of monoclonal immunoglobulin (Ig)-producing neoplastic plasma cells. Large quantities of unfolded or misfolded Ig production may trigger considerable endoplasmic reticulum stress. Thus, MM is originally a fragile neoplasm particularly susceptible to autophagy-, proteasomeand histone deacetylase 6-inhibitors. Taken together, CAM plays an important role in MM treatments through its synergistic mechanisms. In addition, CAM with its pleiotropic effects on cytokines including IL-6 and indirect antiviral effects might be worth a try for treating COVID-19.

The bone marrow of a 53-year-old woman with acute myeloid leukemia (AML) with disseminated intravascular coagulation was investigated by transmission electron microscopy. The patient had a preceding granulocytic sarcoma, and subclinical disseminated intravascular coagulation occurred concomitantly with the development of AML. Ultrastructural findings of the bone marrow at the onset of AML revealed the following: (1) The cytoplasm of the leukemic cells showed frequent fragmentation, resulting in the formation of abundant cytoplasmic fragments. (2) These cytoplasmic fragments were surrounded by abundant fibrin fibers, forming the fibrin-cytoplasmic fragment complex (FCF complex). (3) Slight fibrin deposition was seen around the leukemic cells and in the intercellular space of the bone marrow. Fibrin deposition in the bone marrow is thought to represent morphologic evidence of disseminated intravascular coagulation. The damage on the leukemic cell surface due to the cytoplasmic fragmentation seems to be closely related to the development of disseminated intravascular coagulation.