Systemic lupus erythematosus and myelofibrosis

doi:10.1016/0002-9343(86)90373-6

The American Journal of Medicine

Volume 81, Issue 5, November 1986, Pages 935-938

https://doi.org/10.1016/0002-9343(86)90373-6 Get rights and content

Abstract

Acute thrombocytopenia developed in a 27-year-old woman with systemic lupus erythematosus (SLE). Antibodies to red cells and granulocytes were identified in addition to an increase in platelet, associated IgG. Serum complement levels were reduced, circulating immune complexes were present, and high titers of antinuclear antibodies and antibodies to native DNA were demonstrated. Attempts to aspirate bone marrow were unsuccessful due to an increase in marrow reticulin. Treatment with corticosteroids reversed the thrombocytopenia but not the myelofibrosis or the serologic abnormalities. A review of the literature revealed four other patients, two men and two women, with SLE and myelofibrosis. In two of these patients, the myelofibrosis regressed following therapy with corticosteroids.

References (30)

PJ Fialkow et al.
Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell
Blood
(1981)
CM Lewis et al.
Immune complexes in myeloproliferative disorders
Lancet
(1977)
BR Gordon et al.
Immunologic abnormalities in myelofibrosis with activation of the complement system
Blood
(1981)
DR Budman et al.
Hematologic aspects of systemic lupus erythematosus
Ann Intern Med
(1977)
AG Mowat
Connective tissue diseases
Clin Haematol
(1972)
R Burkhardt
The bone marrow in systemic lupus erythematosus
Semin Hematol
(1965)
J Cavalcant et al.
Red-cell hypoplasia and increased bone marrow reticulin in systemic lupus erythematosus; reversal with corticosteroid therapy
Am J Hematol
(1978)
KS Lau et al.
Myelosclerosis associated with systemic lupus erythematosus in patients in West Malaysia
J Clin Pathol
(1969)
HM Daly et al.
Myelofibrosis as a cause of pancytopenia in systemic lupus erythematosus
J Clin Pathol
(1983)
AA Nanji et al.
Myelofibrosis as a cause of pancytopenia in systemic lupus erythematosus
J Clin Pathol
(1984)

DM McCarthy

Fibrosis of the bone marrow: content and causes

Br J Haematol

(1985)

JL Spival et al.

Hematologic abnormalities in AIDS

Am J Med

(1984)

GJ Den Ottolander et al.

Megakaryoblastic leukemia (acute myelofibrosis): a report of three cases

Br J Haematol

(1979)

RJ Jacobson et al.

Agnogenic myeloid metaplasia

JW Adamson et al.

Polycythemia vera: stem cell and probable clonal origin of the disease

N Engl J Med

(1976)

Cited by (45)

Substance P and fibrotic diseases
2019, Neuropeptides
Citation Excerpt :
At present, it is unclear whether fibrosis is secondary to immune dysfunction or vice versa. However, in patients with autoimmune diseases and myelofibrosis, treatment with immunosuppressive therapy resulted in the reversal of fibrosis (Kaelin and Spivak, 1986). SP, as a proinflammatory cytokine, has been demonstrated to play an important role in the pathophysiology of myelofibrosis.
Substance P (SP) is an undecapeptide encoding the tachykinin 1 (TAC1) gene and belongs to the tachykinin family. SP is widely distributed in the central nervous system and the peripheral nervous system. SP is also produced by nonneuronal cells, such as inflammatory cells and endothelial cells. The biological activities of SP are mainly regulated through the high-affinity neurokinin 1 receptor (NK-1R). The SP/NK-1R system plays an important role in the molecular bases of many human pathophysiologic processes, such as pain, infectious and inflammatory diseases, and cancer. In addition, this system has been implicated in fibrotic diseases and processes such as wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, and lung fibrosis. Recently, studies have shown that SP plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of fibrosis. NK-1R receptor antagonists could provide clinical solutions for fibrotic diseases. This review summarizes the structure and function of SP and its involvement in fibrotic diseases.
Lessons learned from bone marrow failure in systemic lupus erythematosus: Case reports and review of the literature
2018, Seminars in Arthritis and Rheumatism
In the present review, four new cases of bone marrow failure are presented and the potential contribution of systemic lupus erythematosus (SLE) is discussed. Furthermore, a comprehensive literature review of cases of autoimmune myelofibrosis (AIMF), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH) with concurrent SLE aims to allow their direct comparison. Based on a clearer characterization of reported cases and our own experience, diagnostic and therapeutic strategies of these disorders in SLE are proposed based on lessons learned from the present and previous cases.
A literature search was done in PubMed, accessed via the National Library of Medicine PubMed interface (http://www.ncbi.nlm.nih.gov/pubmed). Using PubMed, a Boolean search of the literature was performed by crossing the keywords "systemic lupus erythematosus," AND ["bone marrow fibrosis" or "bone marrow failure" or "myelofibrosis" or "aplastic anemia" or "paroxysmal nocturnal hemoglobinuria"].
After a stringent selection of previous cases with a clear diagnosis of SLE, we summarized in the present review 31 cases of AIMF, 26 cases of AA, and 3 cases of PNH. In addition, four new cases illustrate the problem of attribution of bone marrow failure to SLE.
The attribution of SLE to bone marrow failure is challenging due to a lack of biomarkers, which complicates treatment decisions. Autoimmune myelofibrosis is likely underreported, but corticosteroids and intravenous immunoglobulin appear to be effective immediate therapies. In AA attributable to SLE, a serum inhibitor of bone marrow precursors should be tested, since plasma exchange has been universally successful in these cases, and a PNH clone should be tested for in the setting of ongoing hemolysis, as complement inhibition may be effective. Further research is warranted to elucidate pathophysiological mechanisms of bone marrow failure in SLE.
Autoimmune myelofibrosis: An update on morphologic features in 29 cases and review of the literature
2014, Human Pathology
Citation Excerpt :
Primary AIMF refers to AIMF cases in which patients have autoantibodies but do not have a well-characterized autoimmune disorder. Although isolated case reports have been published, it remains a poorly recognized disorder [1-24]. Various benign and malignant disorders can cause or be associated with a diffuse increase in bone marrow reticulin fibrosis.
Autoimmune myelofibrosis (AIMF) is a distinct clinicopathological entity associated with diffuse bone marrow fibrosis and a benign clinical course. Distinction from neoplastic etiologies of marrow fibrosis, particularly primary myelofibrosis, is imperative, but few studies have documented histopathologic features in a large series. We describe 29 patients with AIMF, defined as marrow reticulin fibrosis and lymphocytic infiltration in the context of an established autoimmune disorder (secondary AIMF) or autoantibodies without a defined disorder (primary AIMF). Excluded were cases with atypical megakaryocytes, dysplasia, basophilia, osteosclerosis, unexplained splenomegaly, or neoplasms associated with myelofibrosis (MF). All cases were stained for reticulin, CD3, and CD20, with a subset additionally stained for CD138, κ, λ, immunoglobulin G (IgG), and IgG4. Lymphoid aggregates, where present, were classified into T-cell and B-cell patterns of distribution. Most patients (93%) presented with cytopenias. Sixty-nine percent (n = 20) were considered secondary AIMF and the remainder primary AIMF (n = 9). Peripheral blood showed absent-to-rare blasts and teardrop erythrocytes and absence of eosinophilia or basophilia. Characteristic bone marrow findings included hypercellularity with erythroid and megakaryocytic hyperplasias, mild reticulin fibrosis, intrasinusoidal hematopoiesis, T-cell pattern in lymphoid aggregates, mild polytypic plasmacytosis, and absence of IgG4-positive plasma cells. Primary and secondary AIMF were pathologically indistinguishable, except for an increased incidence of granulocytic hyperplasia in primary AIMF. This series confirms and expands the utility of the original diagnostic criteria for AIMF. Recognizing the characteristic morphology of AIMF and its associated clinical and laboratory features distinguishes autoimmune from neoplastic causes of MF and guides further evaluation and management.
Bone and joints in haematological malignancies (myeloma excluded)
2005, EMC-Rhumatologie-Orthopedie
L'atteinte osseuse au cours des lymphomes est un événement rare, en dehors des leucémies/lymphomes associés à human T-cell lymphoma virus (HTLV)-I. Il s’agit de lésions ostéolytiques préférentiellement localisées sur la métaphyse des os longs ou le squelette axial. La survenue d'une localisation osseuse reflète l'évolutivité du lymphome, dont le pronostic reste lié à son type histologique et à son extension. La survenue de lésions osseuses au cours de certains syndromes lymphoprolifératifs, leucémie lymphoïde chronique ou maladie de Waldenström, ou de syndromes myéloprolifératifs, peut traduire une transformation en lymphome plus agressif, dont le pronostic reste alors très réservé. L'existence de rares localisations osseuses spécifiques ne doit bien sûr pas faire méconnaître les complications infectieuses des hémopathies malignes, ostéite ou ostéomyélite, chez des sujets immunodéprimés. Les manifestations articulaires des hémopathies malignes sont le plus souvent liées à un processus infectieux (arthrite infectieuse), ou métabolique (goutte). Les arthrites spécifiques sont l’apanage des leucémies aiguës. Des manifestations articulaires secondaires à une vascularite principalement leucocytoclasique sont surtout fréquentes dans les leucémies à tricholeucocytes. Mais ces manifestations ont été rapportées dans toutes les hémopathies malignes, qu’elles peuvent parfois précéder. La connaissance de ces manifestations osseuses et articulaires est importante dans le diagnostic des douleurs osseuses et des arthrites, et il faudra évoquer la possibilité d’une hémopathie en l’absence de réponse aux traitements usuels, en présence de signes systémiques tels qu’une fièvre ou un syndrome inflammatoire persistant, ou de lésions radiologiques atypiques.
Bone involvement is a rare event in lymphomas, except in patients with adult T-cell leukaemia/lymphoma associated with HTLV-I. It is usually characterised by lytic bone lesions located in the metaphysis of long bones or in the axial skeleton. The occurrence of bone lesions reflects a progression of the disease, affecting the prognosis that is related to lymphoma histologic features and staging. Bone lesions may occur in some lymphoproliferative disorders such as LLC or Waldenström’s disease, or in myeloproliferative disorders. They may reflect a progression to a more aggressive disorder with a worse prognosis. Specific bone lesions are rare, and other diagnoses should be entertained, including osteitis or osteomyelitis precipitated by immunodeficiency. Joint involvement in haematological malignancies is most of the time related to infectious complications such as septic arthritis, or to metabolic disorders such as gout. Arthritis related to leukaemic synovitis is a well-recognized complication of leukaemia in children, but acute and chronic leukaemia may also cause arthritis in adults. Vasculitic syndromes, primarily cutaneous leucocytoclastic vasculitis, associated with arthralgias or arthritis, have been described in association with haematological malignancies, especially in hairy cell leukaemia, and may antedate their diagnosis. Haematological malignancies are important to consider in the diagnosis of bone pain or arthritis, and should be suspected particularly in presence of radiological abnormalities, in presence of fever or persistent inflammation in blood tests, as well as in cases of unexplained arthritis, refractory arthritis, or arthritis accompanied by severe pain.
Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis
2001, Blood
Citation Excerpt :
Although the underlying cause of this subgroup is undefined, fibrosis could develop as a secondary process. The second is BM fibrosis, which occurs as a secondary process at various times after the initial diagnosis of polycythemia vera, essential thrombocythemia, chronic myeloid leukemia,2,8–10 myeloma,11lymphoma, and, infrequently, other nonhematologic disorders.12,13 The mechanism of BM fibrosis remains mostly undefined.
Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions—angiogenesis, fibroblast proliferation, and stimulation of BM progenitors—are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 ±12 vs 18 ±3; P < .01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research.
Myelofibrosis in systemic lupus erythematosus: A new case
2000, European Journal of Internal Medicine

View all citing articles on Scopus

View full text

Systemic lupus erythematosus and myelofibrosis

Abstract

Blood

Lancet

Blood

Hematologic aspects of systemic lupus erythematosus

Ann Intern Med

Connective tissue diseases

Clin Haematol

The bone marrow in systemic lupus erythematosus

Semin Hematol

Red-cell hypoplasia and increased bone marrow reticulin in systemic lupus erythematosus; reversal with corticosteroid therapy

Am J Hematol

Myelosclerosis associated with systemic lupus erythematosus in patients in West Malaysia

J Clin Pathol

Myelofibrosis as a cause of pancytopenia in systemic lupus erythematosus

J Clin Pathol

Myelofibrosis as a cause of pancytopenia in systemic lupus erythematosus

J Clin Pathol

Fibrosis of the bone marrow: content and causes

Br J Haematol

Hematologic abnormalities in AIDS

Am J Med

Megakaryoblastic leukemia (acute myelofibrosis): a report of three cases

Br J Haematol

Agnogenic myeloid metaplasia

Polycythemia vera: stem cell and probable clonal origin of the disease

N Engl J Med