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Background
Mixed connective tissue disease is an autoimmune disease which has overlap findings with many autoimmune diseases including SLE, systemic sclerosis, and polymyositis. In contrast to other autoimmune diseases, the absence of severe renal disease and central nervous system disease is characteristic. There is still controversy over the uniqueness of this disease since some cases have evolved to a classic systemic sclerosis.
SYNONYMS MCTD AGE RANGE-MEDIAN 2-3rd decades Women favored
PATHOGENESIS CHARACTERIZATION Clinical and immunological aspects of autoantibodies to RA33/hnRNP-A/B proteins--a link between RA, SLE and MCTD.
Steiner G, Skriner K, Hassfeld W, Smolen JS.
Ludwig Boltzmann-Institute for Rheumatology and Balneology, University of Vienna, Austria.
Mol Biol Rep 1996;23(3-4):167-71 Abstract quote
Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are major constituents of the spliceosome. They are composed of approximately 30 different proteins which can bind to nascent pre-mRNA. Among these, the hnRNP-A/B proteins form a subgroup of highly related proteins consisting of two adjacent RNA binding domains (RBD) within the N-terminal parts, whereas the C-terminal halves contain almost 50% glycine residues. These proteins, in particular A2/RA33, are targeted by autoantibodies from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). In SLE anti-hnRNP antibodies frequently occur together with antibodies to U1 small nuclear RNP (U1-snRNP) and Sm, other proteins of the spliceosome. Preliminary epitope mapping studies have revealed major antibody binding sites in the RNA binding regions for all three diseases. Nevertheless, there is some indication of disease specific epitope recognition. Studies in animal models have demonstrated anti-RA33/hnRNP-A/B antibodies in lupus-prone mouse strains.
Thus, autoantibodies to the spliceosomal hnRNP-A/B proteins are a common feature of RA, SLE, and MCTD. However, these diseases differ in their reactivities to other spliceosomal proteins, especially anti-U1 snRNP and Sm. Therefore, anti-RA33/hnRNP-A/B autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenesis of rheumatic autoimmune diseases.
DISEASE ASSOCIATIONS CHARACTERIZATION Raynaud's phenomenon Fever Pleurisy Pulmonary hypertension Most common cause of death Esophageal dysmotility Myositis Cardiac conduction disturbances in mixed connective tissue disease.
Rebollar-Gonzalez V, Torre-Delgadillo A, Orea-Tejeda A, Ochoa-Perez V, Navarrete-Gaona R, Asensio-Lafuente E, Dorantes-Garcia J, Narvaez R, Rangel-Pena AM, Hernandez-Reyes P, Oseguera-Moguel J.
Rev Invest Clin 2001 Jul-Aug;53(4):330-4 Abstract quote
BACKGROUND: Myocardial involvement occurs in about 20% of patients with mixed connective tissue disease. The purpose of this study was to determine the prevalence of conduction disturbances, their association with other manifestations of the disease.
OBJECTIVE: Determine the prevalence of cardiac conduction disturbances in patients with mixed connective tissue disease attended in an institute in Mexico City and their relation with other manifestations of the disease.
METHODS: One hundred thirteen patients admitted to the Institute with a diagnosis of mixed connective tissue disease were divided into those with conduction disturbances (n = 23) and those without (n = 90). Over a mean follow-up of 10.2 +/- 7.8 years, clinical course, treatment, duration of the disease, types of conduction disturbances and systemic alterations were examined.
RESULTS: There was an overwhelming predominance of women in both groups. Conduction disturbances occurred in about 20% of the patients with mixed connective tissue disease and that was not possible to find significant differences in the outcome of them. As could be expected a significant difference between the two groups was QRS axis, related to anterior hemiblock, the most common conduction alteration observed. During the follow-up one patient death in-group A, but none in group B.
CONCLUSION: Conduction disturbances were present in 20%; in agree with other authors in the literature. However, did not participate in the outcome of the disease.
Mixed connective tissue disease following interstitial cystitis.
Seishima M, Shimizu H, Oyama Z, Isogai K.
Department of Dermatology, Ogaki Municipal Hospital, Minaminokawa-cho, 4-86, Ogaki, 503-8502, Japan.
Eur J Dermatol 2001 Jan-Feb;11(1):45-7 Abstract quote
A 64-year-old woman complained of severe infrapubic pain and pollakisuria with nausea, vomiting and diarrhea, but with normal urinalysis since 1987.
The clinical diagnosis of interstitial cystitis (IC) was made, and cystectomy was performed in 1996. The bladder taken was markedly shrunken with a capacity of 50 ml, and showed bleeding on the mucosal surface. Histological findings of the bladder showed ulcer formation in the mucous membrane, and marked infiltration of mononuclear cells, edema and fibrosis in the submucosal tissue. She had noticed exudative erythema, swelling and sclerosis on the bilateral fingers and dorsal aspects of the hands since 1993, and Raynaud's phenomenon and morning stiffness of the fingers from November, 1998. Laboratory data showed positive anti-nuclear antibody (titer: 1: 2,560) and anti-U1 RNP antibody (titer: 69.5 by ELISA). A diagnosis of mixed connective tissue disease following IC was made.
Pregnancy outcome in nephrotic syndrome with mixed connective tissue disease.
Horita Y, Tsunoda S, Inenaga T, Kawano Y, Ishibashi-Ueda H, Chiba Y, Takishita S.
Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, Osaka, Japan.
Nephron 2001 Nov;89(3):354-6 Abstract quote
We describe two pregnancies of a young woman with mixed connective tissue disease.
In June 1983, she was diagnosed as having Raynaud's phenomenon, arthralgia, and proteinuria. She then developed nephrotic syndrome. Methylprednisolone was initially prescribed at a large dose of 1 g/day which was slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies (the first beginning in December 1988 and the second in May 1992), the patient was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born healthy at term with no complications.
Continuing prednisolone may be useful in pregnant women, and aggressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy.
LABORATORY/RADIOLOGIC/OTHER STUDIES CHARACTERIZATION RADIOLOGIC Pulmonary involvement in mixed connective tissue disease: high-resolution CT findings in 41 patients.
Kozuka T, Johkoh T, Honda O, Mihara N, Koyama M, Tomiyama N, Hamada S, Nakamura H, Ichikado K.
Department of Radiology, Osaka University Medical School, Suita, Japan.
J Thorac Imaging 2001 Apr;16(2):94-8 Abstract quote
The objective of this study was to describe the pulmonary abnormalities on high-resolution computed tomography (CT) in patients with mixed connective tissue disease (MCTD).
The study included 41 patients who met the diagnostic criteria for MCTD and showed abnormal findings on high-resolution CT. The presence, extent, and distribution of various high-resolution CT findings were evaluated. The predominant abnormalities included areas of ground-glass attenuation (n = 41), subpleural micronodules (n = 40), and nonseptal linear opacities (n = 32). Other common findings included peripheral predominance (n = 40), lower lobe predominance (n = 39), intralobular reticular opacities (n = 25), architectural distortion (n = 20), and traction bronchiectasis (n = 18). Less common findings included honeycombing, ill-defined centrilobular nodules, airspace consolidation, interlobular septal thickening, thickening of bronchovascular bundles, bronchial wall thickening, bronchiectasis, and emphysema.
Pulmonary involvement of MCTD is characterized by the presence of ground-glass attenuation, nonseptal linear opacities, and peripheral and lower lobe predominance. Ill-defined centrilobular opacities were uncommonly seen.
LABORATORY Antiphospholipid antibodies in mixed connective tissue disease.
Doria A, Ruffatti A, Calligaro A, Del Ross T, Ghirardello A, De Zambiasi P, Gambari P.
Division of Rheumatology, University of Padova, Italy.
Clin Rheumatol 1992 Mar;11(1):48-50 Abstract quote
We studied the prevalence and clinical significance of antiphospholipid antibodies (ab) in 28 patients affected with well-defined mixed connective tissue disease (MCTD). Forty-two patients affected with systemic lupus erythematosus (SLE) and 60 healthy subjects were also evaluated, as controls.
In MCTD the prevalence of anticardiolipin (aCL) ab was: IgG high level 17.8% (p less than 0.01 versus healthy controls), IgG low level 7.1% and IgM high level 7.1%. No patients had low level of aCL IgM, lupus anticoagulant or false positive VDRL.
The aCL profile was similar to that found in SLE patients, but in SLE all prevalences were higher than in MCTD. Furthermore, in MCTD patients the aCL ab were correlated with thrombocytopenia but not with recurrent thrombosis and/or abortions.
Blotting patterns of IgG anti-(U1)RNP antibodies in mixed connective tissue disease.
Ghirardello A, Doria A, Vesco P, Vaccaro E, Bernardi C, Catani C, Fagiolo U, Gambari PF.
Division of Rheumatology, University of Padova, Italy.
Rheumatol Int 1996;16(4):145-50 Abstract quote
Serum reactivities towards individual U1 snRNP proteins were determined by immunoblotting in 32 patients with mixed connective tissue disease (MCTD).
Time persistence of immunoblot profiles and clinical significance of anti-(U1)RNP antibody specificities were also investigated. IgG anti-(U1)RNP antibodies were found in the sera of 29 out of 32 patients (90.6%): 21 (65.6%) reacted with the 70-kD protein, 25 (78.1%) with A, 23 (71.9%) with C and 20 (62.5%) with B/B' proteins. None were reactive with the Sm-D peptide. Seventy kilodalton antibody specificity was strongly associated with a higher antinuclear antibody titre (> 160) and slightly associated with disease activity; anti-B/B' specificity was associated with lymphadenopathy. Anti-A, -C and -B/B' antibodies were negatively associated with systemic lupus erythematosus (SLE) skin rashes.
Two types of anti-(U1)RNP blotting patterns were selected: "full spectrum" (53.1% of cases) and a "partially/no reactive" one (46.9%). Such patterns were unchanged over time in 14 out of 16 cases prospectively examined (87.5%), while the pattern shifted from "full spectrum" to "partially/no reactive" in 2 cases (12.5%): in 1 after a prolonged clinical remission (> or = 4 years) and in the other following immunosuppressive therapy. The anti-(U1)RNP antibody immunoblot profile in MCTD patients consisted of various reactivities and remained unchanged over time in most cases. Antibody reactivity against the 70-kD protein represented the major U1 snRNP specificity. The various anti-(U1)RNP specific reactivities demonstrated poor clinical significance within MCTD.
Thus, MCTD seems to be characterized by a longstanding serological heterogeneity whose reactivities do not apparently correspond to distinct features within the broad clinical spectrum of MCTD.
Antiphospholipid antibodies among anti-U1-70 kDa autoantibody positive patients with mixed connective tissue disease.
Komatireddy GR, Wang GS, Sharp GC, Hoffman RW.
Department of Internal Medicine, University of Missouri, Columbia 65212, USA.
J Rheumatol 1997 Feb;24(2):319-22 Abstract quote
OBJECTIVE: The association between antiphospholipid antibodies (aPL) and recurrent venous and/or arterial thrombotic events, fetal loss, and thrombocytopenia in systemic lupus erythematosus (SLE) has been well documented. Such an association has not been carefully assessed in mixed connective tissue disease (MCTD). Our aim was to assess the prevalence and clinical significance of aPL in anti-U1-70 kDa autoantibody positive patients with MCTD.
METHODS: We compared 48 consecutive anti-U1-70 kDa autoantibody positive patients with MCTD versus 59 consecutive anti-U1-70 kDa autoantibody negative patients with SLE to determine the frequency of aPL and clinical features of the aPL syndrome.
RESULTS: Among the patients with MCTD 7/48 (15%) had anticardiolipin antibodies (aCL) versus 24/59 (41%) patients with SLE (p < 0.005) and versus 2/150 (1%) apparently healthy blood donors (p < 0.001). Among patients with MCTD with aPL, 2 were IgG, 3 IgM, and 2 both IgG and IgM isotypes; among patients with SLE 5 were IgG, 11 IgM, and 8 both IgG and IgM isotypes. No clotting events or other features of the aPL syndrome were found among the patients with MCTD compared with 26 events documented among the group of aCL positive patients with SLE (p < 0.001). There were 10 patients with SLE with deep vein thrombosis, one with a pulmonary embolism, 2 with recurrent fetal loss, one with chorea, 2 with livedo reticularis, one with severe thrombocytopenia, and one with avascular necrosis.
CONCLUSION: aCL were increased in patients with MCTD compared to controls. Furthermore, aCL were increased in SLE compared with both patients with MCTD and controls. Finally, while clotting events and other manifestations of the aPL syndrome occurred among the group of aCL positive patients with SLE these were distinctly absent from the aCL positive MCTD group.
Quantitative radioligand assays using de novo-synthesized recombinant autoantigens in connective tissue diseases: new tools to approach the pathogenic significance of anti-RNP antibodies in rheumatic diseases.
Yamamoto AM, Amoura Z, Johannet C, Jeronimo AL, Campos H, Koutouzov S, Piette JC, Bach JF.
Hopital Necker, Paris, France.
Arthritis Rheum 2000 Mar;43(3):689-98 Abstract quote
OBJECTIVE: To describe new assays for the detection and quantification of antibodies to RNPs in rheumatic diseases, using soluble nuclear antigens synthesized de novo in reticulocyte lysates.
METHODS: Sera from 381 patients with various rheumatic diseases, including 212 patients with systemic lupus erythematosus (SLE), were analyzed in order to evaluate the sensitivity and specificity of serum autoantibody reactivities to several recombinant soluble autoantigens: U1-A RNP, Sm-B, SSA/Ro 52 and SSA/Ro 60, SSB/La, and Ku. Radioligand assays (RLAs) were performed following the in vitro transcription and translation of each autoantigen from the corresponding complementary DNA, labeled with 35S-methionine. The radiolabeled protein was then bound by the specific serum autoantibody, forming immune complexes that were captured by protein A-Sepharose beads and quantified by counting the radioactivity.
RESULTS: Among the SLE patients, 44% were positive for anti-U1-A RNP activity, 34% for anti-Sm-B, 44% for anti-SSA (32% for Ro 52 and 46% for Ro 60), 32% for anti-SSB/La, and 11% for anti-Ku reactivities. SSA antibodies had a high frequency in patients with mixed connective tissue disease (MCTD) (80%); 65% of these patient sera reacted with Ro 52, 45% with Ro 60, and 45% with U1-A RNP. Twenty percent of the MCTD patients also exhibited antibodies to Sm-B and Ku. In patients with Sjogren's syndrome, anti-SSA was the main anti-RNP antibody (63%), together with SSB/La antibodies (44%). Among patients with inflammatory myopathy, only antibodies against Ro 52 (36%) and Ro 60 (36%) were present. These new RLA allowed observation of a strong correlation (P < 0.0001) between Sm-B antibody levels and the severity of SLE (as measured by the SLE Disease Activity Index), and establishment of a correlation between anti-U1-A RNP antibodies and the occurrence of SLE nephritis (P < 0.02). All RLAs were highly specific for the antigen tested and displayed, in the disease groups studied, a higher sensitivity than conventional immunodiffusion assays.
CONCLUSION: These highly sensitive, specific, and quantitative RLAs represent new tools for the detection of autoantibodies to RNP antigens in rheumatic diseases, and may be useful for (differential) diagnosis in clinical practice.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION General Pediatric Clinical features of patients with juvenile onset mixed connective tissue disease: analysis of data collected in a nationwide collaborative study in Japan.
Kotajima L, Aotsuka S, Sumiya M, Yokohari R, Tojo T, Kasukawa R.
Division of Clinical Immunology, International Medical Center of Japan, Tokyo, Japan.
J Rheumatol 1996 Jun;23(6):1088-94 Abstract quoteOBJECTIVE: To analyze the clinical features and outcome of juvenile-onset mixed connective tissue disease (MCTD).
METHODS: Clinical and laboratory findings were compared in 2 groups of MCTD patients divided according to age at onset: juvenile onset: under 16 yrs: adult onset: 16 yrs or older).
RESULTS: Systemic lupus erythematosus-like symptoms, such as facial erythema, photosensitivity. LE cells, lymphadenopathy, and cellular casts, were more frequent in juvenile onset MCTD than in the adult form of the disease. On the other hand, scleroderma-like symptoms, such as esophageal hypomotility, scleroderma-like lesions evident on skin biopsy, pulmonary involvement, proximal scleroderma, and pitting scars, were less frequent in juvenile onset MCTD than in the adult form. Patients with juvenile onset MCTD more frequently met the classification criteria for systemic lupus erythematosus (SLE) and less frequently met those for progressive systemic sclerosis (SSc), compared to patients with adult onset MCTD. At disease onset, hand edema and stiffness were observed less frequently in juvenile onset MCTD than in the adult form. Furthermore, the mortality rate was lower in the former than in the latter (2.8% vs 8.4%).
CONCLUSION: Although previous studies have reported severe symptoms and adverse outcome for juvenile onset MCTD, we conclude from this nationwide study in Japan that patients with juvenile onset MCTD exhibit more SLE-like and fewer SSc-like features and have a relatively favorable outcome.
Mixed connective tissue disease in childhood: a nationwide retrospective study in Japan.
Yokota S, Imagawa T, Katakura S, Itoh SI, Mitsuda T, Fujikawa S, Aihara Y.
Department of Pediatrics, Yokohama City University School of Medicine, Japan.
Acta Paediatr Jpn 1997 Apr;39(2):273-6 Abstract quote
Sixty-six children with mixed connective tissue disease (MCTD) were analyzed by a nationwide prospective study.
The diagnostic significance of Raynaud's phenomenon and positive anti-RNP antibody was confirmed, and additional symptoms including swelling of fingers, facial erythema, and polyarthralgia, and laboratory findings such as positive rheumatoid factor, hypergammaglobulinemia, and increased levels of myogenic enzymes, were variably positive.
These clinical and laboratory characteristics of MCTD were critically different from those of systemic lupus erythematosus, indicating that MCTD is an independent entity of disease.
VARIANTS SKIN Nonscarring diffuse alopecia common Pigmentary alteration with follicular retention of pigment in 67% of patients Sclerodactyly with sausage-like swelling of the digits Sclerodermiform nailfold capillaropathy Heliotrope eyelids Gottron's papules
HISTOLOGICAL TYPES CHARACTERIZATION General VARIANTS Am J Dermatopathol 1997;19:206-213
Lichenoid interface dermatitis with striking colloid body formation, lymphocyte satellitosis around necrotic keratinocytes, orthohyperkeratosis, and dermal mucin deposition
Prominent vasculopathic alterations with vascular ectasia, hypovascularity, and luminal thrombosis limited to superficial vascular plexus
Occasional sclerodermoid changes of the collagen
No deep perivascular or periadnexal lymphocytic infiltrate
Lacked follicular pluggingLUNGS Severe pulmonary involvement in mixed connective tissue disease.
Wiener-Kronish JP, Solinger AM, Warnock ML, Churg A, Ordonez N, Golden JA.
Am Rev Respir Dis 1981 Oct;124(4):499-503 Abstract quote
Pulmonary involvement in mixed connective tissue disease has been considered a benign manifestation that is easily treated with corticosteroids.
We followed 5 patients who had mixed connective tissue disease and severe, rapidly progressive, lung disease. Two types of lung disease were found, interstitial lung disease and pulmonary hypertension.
Histologic sections from our patients were compared with sections from patients who had interstitial lung disease and systemic lupus erythematosus or pulmonary hypertension and scleroderma. Although clinical presentations were similar, the immunofluorescent and electron microscopic findings for interstitial lung disease were somewhat different in patients with systemic lupus erythematosus. Histologic findings for pulmonary hypertension appeared different in patients with mixed connective tissue disease and patients with scleroderma.
For patients with either type of lung disease, corticosteroid therapy proved inadequate, but nearly cytotoxic therapy may be beneficial.
Mixed connective tissue disease with fatal pulmonary hypertension and a review of literature.
Ueda N, Mimura K, Maeda H, Sugiyama T, Kado T, Kobayashi K, Fukuzaki H.
Virchows Arch A Pathol Anat Histopathol 1984;404(4):335-40 Abstract quote
The paper presents an autopsy case of mixed connective tissue disease (MCTD) with pulmonary hypertension (PH) and a review of literature.
A 33-year-old woman with Raynaud's phenomenon and dyspnea of one year duration was diagnosed as having MCTD on the basis of a higher titer (1:163,840) of serum antibodies to the ribonucleoprotein (RNP). Cardiac catheterization showed complicating PH, confirmed an autopsy by the findings of concentric intimal cellular proliferation and typical plexiform lesions in the small arteries and arterioles of the lung, suggesting primary PH.
Fatal PH with MCTD has been reported only 6 cases in literature including our case. All were young females, with histopathological findings consistent with plexogenic pulmonary arteriopathy in 5 cases and with recurrent pulmonary thromboembolism in the other. The aetiology of PH is still unknown, but it may be due to vasoconstriction evoked by the hyper-reactivity of the vessels.
CNS Stroke and mixed connective tissue disease.
Graf WD, Milstein JM, Sherry DD.
Department of Pediatrics, Children's Hospital and Medical Center, University of Washington, Seattle 98105.
J Child Neurol 1993 Jul;8(3):256-9 Abstract quote
We describe the clinical presentation and course of two girls with cerebrovascular disease and mixed connective tissue disease. One developed rapid onset hemiparesis and aphasia secondary to left internal carotid artery occlusion. She experienced a complete recovery after treatment with prednisone and cyclophosphamide. The other patient was diagnosed as having mixed connective tissue disease but had acute neurologic deterioration. She died due to an intracerebral hemorrhage.
Autopsy demonstrated small-vessel fibrinoid necrosis. Although cerebrovascular disease secondary to central nervous system vasculitis is a manifestation of systemic lupus erythematosus, this is the first description of cerebrovascular disease as a primary sign in mixed connective tissue disease.
These cases demonstrate the range of cerebrovascular disease observed in children with mixed connective tissue disease.
SPECIAL STAINS/IMMUNOPEROXIDASE/OTHER CHARACTERIZATION Direct immunofluorescence (DIF) Br J Dermatol 1982;107:653-657
Speckled nuclear staining of epidermal keratinocytes which correlates with high titer of URNP antibodies (IgG)
May have lupus band positive
Terminal complement present along blood vessel wallsIndirect immunofluorescence (IIF) Particulate speckled pattern Absent anti-Sm antibody
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clinical and immunogenetic followup of 46 patients.
Gendi NS, Welsh KI, Van Venrooij WJ, Vancheeswaran R, Gilroy J, Black CM.
Nuffield Orthopaedic Centre, Oxford, United Kingdom.
Arthritis Rheum 1995 Feb;38(2):259-66 Abstract quote
OBJECTIVE. To determine any clinical or genetic markers of differentiation and outcome in a previously described cohort of 46 patients with mixed connective tissue disease (MCTD).
METHODS. Patients were clinically evaluated, chart notes reviewed, and HLA subtyping and immunology profiles performed where possible. Eleven had died and 7 were lost to followup.
RESULTS. MCTD had differentiated into systemic lupus erythematosus in 12 patients and into systemic sclerosis in 13. The latter was associated with HLA-DR5 (P = 0.038), and nondifferentiation was associated with HLA-DR2 or DR4 (P = 0.007). Three HLA-DR4 positive patients had MCTD that evolved into rheumatoid arthritis. Erosive and/or deforming arthritis was associated with HLA-DR1 or DR4 (P = 0.015). HLA-DR3 was associated with interstitial lung fibrosis (P = 0.044) and keratoconjunctivitis sicca (0.001 < P < 0.01). Severe Raynaud's phenomenon predicted higher mortality (0.01 < P < 0.05).
CONCLUSION. We suggest that MCTD is, for most patients, an intermediate stage in a genetically determined progression to a recognized connective tissue disease. Those whose disease remains undifferentiated might be considered a distinct subset.
Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings.
Burdt MA, Hoffman RW, Deutscher SL, Wang GS, Johnson JC, Sharp GC.
University of Missouri, Columbia, USA.
Arthritis Rheum 1999 May;42(5):899-909 Abstract quote
OBJECTIVE: To determine the long-term clinical and immunologic outcomes in a well-characterized cohort of 47 patients with mixed connective tissue disease (MCTD), including reactivity with U small nuclear RNP (snRNP) polypeptides.
METHODS: Patients were followed up over a period of 3-29 years with immunogenetic and systematic clinical and serologic analysis. Sera were analyzed for reactivity with snRNP polypeptides U1-70 kd, A, C, B/B', and D, for anti-U1 RNA, and for anticardiolipin antibodies (aCL).
RESULTS: The typical core clinical features of MCTD tended to develop over time; features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension, pulmonary dysfunction, and central nervous system disease persisted, following treatment. A favorable outcome was observed in 62% of patients; 38% had continued active disease or had died, with death associated with pulmonary hypertension and aCL. All patients had autoantibodies to the U1-70 kd polypeptide of snRNP, and most were positive for anti-U1 RNA. An orderly progression of intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, as was the novel finding of "epitope contraction" followed by disappearance of anti-snRNP autoantibodies during prolonged remission.
CONCLUSION: These patients demonstrated the typical immunogenetic, clinical, and serologic findings of MCTD, and the condition rarely evolved into systemic lupus erythematosus or systemic sclerosis. The majority of patients had favorable outcomes, with pulmonary hypertension being the most frequent disease-associated cause of death. Intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, followed by "epitope contraction" and ultimate disappearance of anti-snRNP autoantibodies during prolonged disease remission.
TREATMENT IMMUNOGLOBULIN Efficacy of pulsed intravenous immunoglobulin therapy in mixed connective tissue disease
Anja Ulmer, MD
Ina Kötter, MD
Andreas Pfaff
Gerhard Fierlbeck, MD
Tübingen, GermanyJ Am Acad Dermatol 2002;46:123-7 Abstract quote
We describe a 69-year-old patient with long-standing mixed connective tissue disease who suffered from severe skin eruptions that did not respond to various immunosuppressive regimens. Therapy with high-dose intravenous immunoglobulin was successful in controlling the patient's disease without major side effects.
We think that this regimen—although expensive—might be an interesting therapeutic option in selected patients with mixed connective tissue disease that is refractory to other treatment modalities.
PLASMAPHERESIS Mixed connective tissue disease with multiple organ damage: successful treatment with plasmapheresis.
Seguchi M, Soejima Y, Tateishi A, Iida H, Yamamoto M, Nakashima K, Murakami F, Ohashi S, Yamashita S, Maekawa T, Murashige A, Umemoto S, Matsuzaki M, Fukumoto Y.
Total Care Unit, Yamaguchi University School of Medicine, Ube.
Intern Med 2000 Dec;39(12):1119-22 Abstract quote
A 24-year-old-woman with mixed connective tissue disease (MCTD) developed multiple organ failure, disseminated intravascular coagulation (DIC), metabolic acidosis, and respiratory and renal failure resulting from visceral vasospasm, so-called visceral Raynaud's phenomenon.
After plasmapheresis, the condition of multiple organ failure was markedly improved. The successful treatment with plasmapheresis was dependent upon the removal of immune complexes in serum and improvement of visceral circulation.
Thus plasma exchange is recommended as a possible a treatment for multiple organ damage in MCTD.
Medicine (Baltimore) 1980;59:239-248
Arch Dermatol 1977;113:583-587
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