Dermato-neuro syndrome after COVID-19 infection in a patient with scleromyxoedema: Previously successful treatment with intravenous immunoglobulins.

Scleromyxedema (SMX) is a rare disease of unknown cause. It is a chronic, progressive, metabolic disorder characterized by a generalized papular and scleroderma-like rash, as well as a subtype of lichen myxedematosus. Dermato-neuro syndrome (DNS) is a rare neurological complication of SMX. It has flu-like prodromal symptoms; consists of a triad of fever, coma, and seizures; and can be life-threatening. We describe a patient with SMX complicated by DNS after infection with COVID-19. Her symptoms resolved after treatment with acyclovir and low-dose glucocorticoids, suggesting that DNS seizures may have a viral cause. Her skin lesions also improved after seven courses of intravenous immunoglobulin treatment, confirming that intravenous immunoglobulin is effective in these cases.

[Dermato-neuro syndrome-an acute and life-threatening complication of scleromyxedema Arndt-Gottron]. / Dermato-neurologisches Syndrom ­ eine akute und lebensbedrohliche Komplikation des Skleromyxödems Arndt-Gottron.

Scleromyxedema Arndt-Gottron is the systemic variant of lichen myxedematosus in which mucin accumulation occurs in the dermis. The disease is usually chronically progressive and extracutaneous manifestations or complications are possible. The pathogenesis is unknown and the disease is usually associated with monoclonal gammopathy. High-dose intravenous immunoglobulins (IVIg) are considered to be an effective therapy. We report the case of a patient who developed dermato-neuro syndrome following an interruption of IVIg treatment and a SARS-CoV­2 infection. A similar episode occurred 2 years earlier in association with an influenza A infection. Dermato-neuro syndrome is a potentially lethal neurological complication which is characterized by fever, delirium, convulsions, and coma.

Generalized Muscular Uptake of 99m Tc-MDP on Bone Scan in a Patient With Scleromyxedema-Associated Myopathy.

ABSTRACT: A 62-year-old man presented with a 5-year history of progressive myasthenia, myalgia, and skin changes. Upon laboratory testing, elevated serum creatine kinase and lactate dehydrogenase, as well as monoclonal immunoglobulin Gκ, were observed. A bone scan revealed generalized muscular uptake of 99m Tc-MDP, whereas 18 F-FDG PET/CT demonstrated only mild hypermetabolism of the muscles. A muscle biopsy showed myofibrillary vacuolar degeneration, and a skin biopsy indicated scleromyxedema. Based on these findings, the patient was diagnosed with scleromyxedema-associated myopathy.

Renal injury in scleromyxoedema due to monoclonal gammopathy associated C3 glomerulonephritis.

Scleromyxoedema is a rare mucinosis that primarily affects the skin. It is associated with monoclonal gammopathy and has many extracutaneous manifestations, however, renal involvement is rare. We report the case of a woman with monoclonal gammopathy and scleromyxoedema presenting with progressive exertional dyspnoea and acute renal failure. Workup of her renal failure revealed monoclonal gammopathy associated C3 glomerulonephritis. She was treated with intravenous steroids and discharged with plans to pursue annual monoclonal gammopathy laboratory monitoring. Given the rarity of renal scleromyxoedema, careful investigation of extracutaneous manifestations and comorbidities is critical to discern the primary pathological process in patients with scleromyxoedema who develop renal insufficiency.

Clinical and histopathological improvement of scleromyxedema-induced microstomia after hyaluronidase injection.

INTRODUCTION: Scleromyxedema is a rare primary cutaneous mucinosis characterized by numerous firm, waxy, confluent papules. Recently, intravenous immunoglobulin (IVIG) is accepted by many authors as the first-line treatment option for severe cases. We report a 69-year-old male patient who has been suffering from scleromyxedema, with reduced mouth opening. He has been on a high-dose IVIG regime for 5 years. METHODS: The patient stated that he had difficulty in wearing and removing his dentures because of reduced mouth opening lately. Before considering to add any other immunosuppressants to his regime, we injected 1500 IU of hyaluronidase in total in one session periorally. The patient has been told open his mouth maximum and photographs have been taken before injections and after one month. We used a photo measurement application when evaluating microstomia to increase accuracy. We also took punch biopsies in order to evaluate effect of hyaluronidase histopathologically before and one month after injections. RESULTS: One month later, he was able to reattach and remove his dentures without adding any adjuvant immunosuppressants other than hyaluronidase. Mouth opening was increased in measurements and histopathologically, mucin deposition, fibroblastic proliferation, and perivascular lymphocytic infiltration were decreased. CONCLUSIONS: We think hyaluronidase is a safe, easily accessible, and effective treatment option for microstomia caused by scleromyxedema.

Successful treatment of dermato-neuro syndrome with plasmapheresis.

Altered mental status can have many causes ranging from emergent intracranial pathologies to more insidious, systemic toxic aetiologies. We report a rare case of dermato-neuro syndrome in a 71-year-old man with a known history of scleromyxoedema. The patient initially presented with encephalopathy which quickly progressed to generalised tonic-clonic seizures and coma. While his presentation fits with other, although rare, cases of dermato-neuro syndrome, it is imperative to rule out lethal, more common causes of altered mentation. Due to the rarity and difficulty in diagnosis of dermato-neuro syndrome, there is a significant debate regarding the optimal management as there are no standardised treatment protocols. In our case, the patient was successfully treated with plasmapheresis resulting in improved neurologic function.

Acute Encephalitic Syndrome Induced by Scleromyxedema.

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.

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 ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Severe but reversible pulmonary hypertension in scleromyxedema and multiple myeloma: a case report.

BACKGROUND: Scleromyxedema is a progressive, systemic connective tissue disorder characterized by fibro-mucous skin lesions and increased serum monoclonal immunoglobulin levels. Pulmonary involvement occurs in a subset of patients, though the overall prevalence of pulmonary lesions in scleromyxedema is unknown. Since pulmonary hypertension presumably occurs in these patients due to disease progression and development of additional conditions, treatment of the underlying plasma cell dyscrasia and connective tissue disorder may improve pulmonary hypertension symptoms. CASE PRESENTATION: An elderly patient with scleromyxedema developed pulmonary hypertension refractory to vasodilator and diuretic therapy and subsequently multiple myeloma that responded to a combination therapy of bortezomib, cyclophosphamide, and dexamethasone treatment. CONCLUSIONS: Treatment of the underlying disease(s) that contributed to pulmonary hypertension development with anti-neoplastic agents like bortezomib may improve cardiopulmonary symptoms secondary to reducing abnormal blood cell counts and paraprotein levels.

Myopathy and scleromyxedema.

Scleromyxedema is a chronic, idiopathic disorder associated with monoclonal gammopathy, and characterized by dermal mucin deposition. However, systemic manifestations are frequent, including neuromuscular symptoms. We herein present a 71-year-old man who developed a vacuolar myopathy in a context of a known scleromyxedema, and we compare our observation with the nineteen other cases found in the medical literature. Such an association (especially with suggestive skin abnormalities) has to be known for two reasons. First, this diagnosis might be quite challenging because the myopathy may precede the typical skin changes. Secondly, conversely to other forms of vacuolar myopathy, some of the symptoms may respond (even partially) to immunomodulatory and/or immunosuppressant therapeutics.

[Scleromyxedema as a systemic disease of glycosaminoglycan accumulation]. / Skleromiksedema kak sistemnaia bolezn' nakopleniia glikozaminoglikanov.

Scleromyxedema is a rare mucinosis with a primary skin lesion due to diffuse mucin deposition, sclerosis, and lichenoid eruptions in the absence of hypothyroidism. The paper describes scleromyxedema cases and gives recommendations for the histological diagnosis of the disease by histochemical reactions to detect acid and neutral glycosaminoglycans.