The association of potentially lethal neurologic syndromes with scleromyxedema (papular mucinosis)

doi:10.1016/0190-9622(93)70021-K

Journal of the American Academy of Dermatology

Volume 28, Issue 1, January 1993, Pages 105-108

https://doi.org/10.1016/0190-9622(93)70021-K Get rights and content

Two patients with scleromyxedema who had progressive neurologic impairment are described. One patient died, and one required prolonged mechanical ventilation. A review of the literature has produced 24 other cases of scleromyxedema in which neurologic changes were prominent.

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Cited by (65)

Monoclonal gammopathy of clinical significance: what the rheumatologist needs to know
2022, The Lancet Rheumatology
Citation Excerpt :
Musculoskeletal involvement can include arthralgias or arthritis of the peripheral joints (especially the hands), proximal or generalised muscle weakness, myopathy, and rarely rhabdomyolysis.20,26,28,30,35,36 A third of patients have neurological manifestations, including carpal tunnel syndrome, peripheral neuropathy, memory loss, vertigo, and gait abnormalities.28,32,36,37 The dermato-neuro syndrome, which consists of fever, confusion, dysarthria, and lethargy, is a rare but important complication that can progress to seizures and coma.20,37
Monoclonal proteins can provide important information on the diagnosis of several non-malignant systemic inflammatory disorders. At low concentration, they most commonly represent monoclonal gammopathy of undetermined significance (MGUS), whereas high concentrations often signify plasma cell myeloma or B-cell lymphoma. However, several rare inflammatory conditions associated with variable concentrations of monoclonal proteins, systemic symptoms, and organ dysfunction also exist. These conditions are termed monoclonal gammopathies of clinical significance (MGCS). Patients with MGCS might present to rheumatologists with undiagnosed systemic inflammatory disorders and the monoclonal protein provides an important, underappreciated clue for diagnosis. In this Review, we provide an approach to distinguishing MGCS from MGUS and lymphoid neoplasms, focusing on four rare MGCS that rheumatologists must recognise: scleromyxedema, Schnitzler's syndrome, idiopathic systemic capillary leak syndrome (also known as Clarkson's disease), and telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting (known as TEMPI) syndrome.
Acute Encephalitic Syndrome Induced by Scleromyxedema
2020, American Journal of the Medical Sciences
Citation Excerpt :
The neurological signs of DNS in our patient were the dominant manifestations of the underlying scleromyxedema disease. Webster et al described 26 patients with scleromyxedema and central nervous system disorders, 9 of which died.11 Another case of scleromyxedema and DNS was published by Fleming et al5 of a 45-year-old male with flu-like symptoms, exacerbation of his skin lesions, and neurological manifestations.
Dermato-neuro syndrome is a potentially fatal neurological complication of scleromyxedema consisting of fever, seizures, and coma. This is an overlooked scleromyxedema case of a 62-year-old female patient from 2-years ago. She was admitted to our ICU because of high fever, colloid speech, muscle ache, and nausea. Molecular methods in the cerebrospinal fluid for neurotropic viruses ruled out acute infectious encephalitis. Her thyroid hormones were within normal values while the serum protein electrophoresis confirmed the monoclonal gammopathy of immunoglobulin G lambda (IgG(λ)), known for the last 2 years. The subsequent bone-marrow biopsy excluded the development of multiple myeloma. The patient fulfilled fundamental diagnostic criteria of scleromyxedema (monoclonal gammopathy, normal thyroid function and the appearance of marked sclerosis and induration of the skin papules on the face, neck, extremities, and skin creases) presenting as dermato-neuro syndrome, which was histologically confirmed. She demonstrated a remarkable improvement after intravenous immunoglobulin treatment during the first 24 hours. Mimics of non-infectious acute encephalitis should include the clinical diagnosis of scleromyxedema, especially when patients present in the emergency department with acute fever, coma, and skin lesions of diffuse sclerodermoid and papular type.
Plasma cell–directed therapies in monoclonal gammopathy–associated scleromyxedema
2020, Blood
Citation Excerpt :
Our series of patients highlights the high frequency of central nervous system injuries in scleromyxedema, especially DNS. DNS usually starts as a “flu-like” syndrome and fever, followed by multiple neurological symptoms, such as convulsions, seizures, and coma.12-15 Other central neurological symptoms have been described without typical DNS features (isolated epilepsy and acute psychosis).
Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell–directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
Dermato-neuro syndrome during scleromyxedema: Efficacy of plasmapheresis and intravenous immunoglobulin
2014, Annales de Dermatologie et de Venereologie
Le dermatoneuro syndrome est une complication neurologique particulière du scléromyxœdème, rapportée une vingtaine de fois dans la littérature médicale. Il associe fièvre, coma, convulsions et syndrome pseudo-grippal. Le devenir des patients atteints est mal connu. Nous décrivons l’observation d’une patiente ayant répondu favorablement à l’association de plasmaphérèses et d’immunoglobulines intraveineuses (IgIV).
Une femme de 57 ans était atteinte de scléromyxœdème évoluant depuis 14 ans, résistant à de multiples thérapeutiques. En novembre 2011, elle présentait un premier épisode de crises convulsives suivi d’un coma post-critique, puis d’un syndrome confusionnel associé à des hallucinations visuelles, spontanément résolutif en quelques jours. La recherche d’une infection était négative et l’imagerie cérébrale (tomodensitométrie et IRM) ainsi que l’électroencéphalogramme étaient parfaitement normaux, soulevant l’hypothèse d’une atteinte neurologique de son scléromyxœdème. En décembre 2012 et août 2013, elle présentait deux nouveaux épisodes d’état de mal épileptique, suivis à nouveau d’un état confusionnel, pour lequel la recherche étiologique était encore négative. Cette fois, l’état confusionnel se pérennisait pendant deux mois, jusqu’à la mise en place des échanges plasmatiques, suivie d’une cure d’IgIV. Cette association thérapeutique permettait d’obtenir une régression rapide de l’ensemble des symptômes neurologiques et une amélioration de l’état général.
Le dermatoneuro syndrome est une complication neurologique centrale rare du scléromyxœdème. Sa physiopathologie est inconnue. La gammapathie monoclonale associée au scléromyxœdème pourrait expliquer un état d’hypercoagulabilité ou la formation d’agrégats neutrophiliques aboutissant à une altération de la microcirculation. Le traitement est empirique et mal codifié. L’évolution est imprévisible et potentiellement létale.
Dermato-neuro syndrome is a specific neurological complication of scleromyxedema presenting with fever, coma, seizures and flu-like syndrome. To our knowledge, it has only been reported about twenty times in the literature. Its outcome is uncertain. We describe the case of a patient in whom a favorable outcome was achieved using a combination of plasmapheresis and intravenous immunoglobulin (IVIG).
A 57-year-old woman was diagnosed 14 years ago with scleromyxedema resistant to multiple lines of treatment. In November 2011, she presented an initial episode of epileptic seizure followed by post-seizure coma, and later, confusional state with visual hallucinations. She recovered spontaneously within a few days. CT scan, MRI, EEG and screening for infection were perfectly normal, resulting in suspicion of neurological involvement associated with her scleromyxedema. In December 2012 and August 2013, she presented two further episodes of status epilepticus, followed once more by a confusional state, with etiological explorations again proving unfruitful. On this occasion, her confusional state persisted for two months until the initiation of plasmapheresis and IVIG. This combination therapy led to rapid regression of all neurological symptoms and an improvement in her general condition.
The dermato-neuro syndrome is a rare neurological complication of scleromyxedema. Its pathophysiology is unknown. The monoclonal gammopathy induced by the scleromyxedema could account for the patient's hypercoagulable state and for the formation of neutrophilic aggregates leading to impaired microcirculation. Treatment is empirical and poorly codified. The course of the disease is unpredictable and may be lethal.
Good response of scleromyxedema and dermato-neuro syndrome to treatment with intravenous immunoglobulins
2012, Actas Dermo-Sifiliograficas
El escleromixedema es una enfermedad potencialmente grave que puede asociarse a complicaciones sistémicas diversas, entre las que se encuentran las que involucran al sistema nervioso central, siendo el síndrome dermato-neuro una de las más infrecuentes. Se han utilizado para su tratamiento fármacos variados, entre ellos, altas dosis de inmunoglobulinas endovenosas. Se describen dos casos de escleromixedema, uno de los cuales desarrolló un síndrome dermato-neuro, ambos con una excelente respuesta al tratamiento con inmunoglobulinas endovenosas. El uso de altas dosis de inmunoglobulinas endovenosas en el tratamiento de esta enfermedad y sus complicaciones neurológicas se perfila como un tratamiento de primera línea.
Scleromyxedema is a potentially serious disease that can have various systemic complications. One of the most frequent forms of central nervous system involvement is dermato-neuro syndrome. High-dose intravenous immunoglobulins are among the drug treatments that have been used for this syndrome. We describe 2 patients with scleromyxedema, one of whom developed dermato-neuro syndrome. Both patients responded well to treatment with high-dose intravenous immunoglobulins. We suggest this therapy as a suitable first-line treatment for scleromyxedema and for its neurological complications.
Corticosteroid-induced Dercum's disease
2011, Dermatologica Sinica

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The association of potentially lethal neurologic syndromes with scleromyxedema (papular mucinosis)

J Am Acad Dermatol

Further observations on lichen myxedematosus

Ann Intern Med

Papular mucinosis

JAMA

Scleromyxedema (lichen myxedematosus) associated with a paraprotein, Ig G, of type kappa

Br J Dermatol

Scleromyxedema: a variant of lichen myxedematosus

Arch Dermatol

Treatment of scleromyxedema with melphalan

Arch Dermatol

Scleromyxedema

Br J Dermatol

Scleromyxedema: therapeutic response to isotretinoin in three patients

J Am Acad Dermatol

Lichen myxedematosus

Arch Dermatol

Mucinose papuleuse du type schlero-myxodeme de Arndt-Gottron

Minerva Dermatol

Plasma cell dyscrasia and peripheral neuropathy with a monoclonal antibody to peripheral nerve myelin

N Engl J Med

Antibodies to gangliosides and myelin proteins in Guillain Barr6 Syndrome

Ann Neuro