Scleroderma-Like Disorders or Pseudoscleroderma Spectrum Diseases
Most articles in the Scleroderma Society Newsletter discuss various topics on systemic sclerosis (SSc), a connective tissue disease that affects the skin and the internal organs. In this issue of the Newsletter I will discuss scleredema and scleromyxoedema, which belong to the scleroderma-like disorders, also called pseudoscleroderma spectrum conditions . They may, in part, resemble SSc and cause diagnostic confusion.
We would like to make members of the Society aware of these very rare conditions, for your information and interest. We do not intend to induce any doubt regarding your current diagnosis.
Scleroderma-like disorders (or pseudoscleroderma spectrum conditions ) are characterised by excessive skin fibrosis but should be differentiated from systemic sclerosis. These conditions include:
• localised forms of scleroderma: morphoea and linear scleroderma.
• fibrosing disorders including: fasciitis with eosinophilia , eosinophilia-myalgia syndrome , toxic oil syndrome , nephrogenic fibrosing dermopathy.
• sclerotic or fibromucinous disorders (see footnote) : scleredema and scleromyxoedema .
Most of you might be familiar with the localised forms of scleroderma or the fibrosing disorders, which are more common than sclerotic or fibromucinous disorders. The latter conditions are extremely rare and their prevalence has not been estimated: frequency was estimated once, in 1965, with 223 cases of scleredema reported worldwide at that time. At the Royal Free Hospital a few patients with scleredema have been followed-up: this short article is dedicated to Patricia, who suffered from scleredema.
Although frequently misdiagnosed as systemic sclerosis, scleroderma-like disorders are distinguishable from SSc by the clinical pattern of skin involvement and the absence of the following : 1) Raynaud's phenomenon, 2) scleroderma-specific autoantibodies, 3) abnormalities of the nailfold capillaries on capillaroscopy 4) internal organ involvement in most patients. Biopsy findings of the involved skin can be similar in scleroderma-like disorders and in systemic sclerosis and therefore skin biopsy is less helpful in differential diagnosis.
Scleredema was first described by Buschke in 1902 [1]; its onset has been linked to acute respiratory tract infection, diabetes mellitus or monoclonal gammopathy (see footnote). Scleredema is characterised by more or less widespread sclerotic skin changes, usually of the neck, shoulders, arms and thighs. The hands are typically spared. Internal organ involvement is extremely rare and it's even debatable if it occurs at all. The course of the disease is usually benign and the prognosis is good, with a spontaneous resolution after a few years. This is good news as, so far, there are no specific therapies that have been found to be effective. However, cases with monoclonal gammopathy can be complicated by malignant haematological conditions such as multiple myeloma (MM) (see footnote) or AL amyloidosis (see footnote).
Scleromyxoedema (also called “ papular mucinosis” ) is characterised by the presence of lichenoid papules (which can be better described as “raised spots that look like the surface of an old rock”) that join together to form “confluent plaques” with extensive skin thickening and hardening. Scleromyxoedema can occur anywhere on the skin, and, unlike scleredema, may also involve the hands. Systemic involvement is extremely rare and even questionable, but some authors have suggested the involvement of the heart, lungs, muscles or of the peripheral nervous system, which means the disease is able to mimic SSc. As for scleredema, there may be an association with diabetes mellitus and monoclonal gammopathy.
The diagnosis of scleroderma-like disorders may be difficult and a clear distinction between scleredema and scleromyxoedema may be tricky. This is because the diagnosis is clinical, as there are neither specific blood tests nor typical findings on skin biopsy. The patients are often mistakenly diagnosed with systemic sclerosis, and, as a result of this, managed inappropriately. In the case of scleredema and scleromyxoedema, regular follow-up and blood testing, in particular the search for monoclonal gammopathy by the laboratory test [called serum protein electrophoresis (see footnote)] are mandatory for early diagnosis of the potentially serious haematological complications mentioned here [2].
Many thanks to Bill Holloway, Patricia's husband.
Dr Magdalena Dziadzio, Azienda Sanitaria Unica Regionale, Marche, Ancona, Italy
References
[1] Buschke A. Über Scleroderm (1902). Berliner Klinische Wochenschrift; 39:955-7.
[2] Dziadzio M, Anastassiades C, Potter M, Hawkins P, Gabrielli A, Brough G, Black C, Denton C. From scleredema to AL amyloidosis: a coincidence or disease progression? Review of the literature, Clin Rheumatol 2005; 24 (3), published online, in press .Fibromucinous disorders represent a group of conditions, where both 1) skin fibrosis and 2) skin deposits of some sugars (called glycosaminoglycans) alone or in the form of mucin (ie in association with proteins called mucoproteins or proteoglycans), are present and make the skin more viscous. These deposits can be revealed by the analysis of the skin (specially prepared, stained and analysed under the microscope).
Monoclonal gammopathy is the presence of an abnormal immunoglobulin (a subclass of the proteins) in the blood. Normal immunoglobulins are necessary for our defence against various infections (mostly of the bacterial origin) and are produced by a subtype of the normal white blood cells called plasma cells. Abnormal, identical (monoclonal) plasma cells produce abnormal immunoglobulin, which is not able to play its role. Some patients with monoclonal gammopathy can progress and develop a condition called multiple myeloma (MM).
Multiple myeloma (MM) is a disease of the blood, caused by the infiltration of the bone marrow (which produces all blood cells: white cells, red cells and the platelets) by the abnormal plasma cells. These cells produce abnormal immunoglobulins described above. These immunoglobulins are then deposited in various internal organs, causing their dysfunction and, in severe cases, their failure. MM can be further complicated by systemic amyloidosis.
Systemic amyloidosis (AL amyloidosis) is a condition where the fragments of the immunoglobulins, also called “light chains”, are present in the circulation; these light chains can be deposited in various organs forming typical insoluble amyloid fibrils, causing organ dysfunction and failure. Most internal organs can be affected but the involvement of the kidneys or of the heart can be fatal. A few therapies available at present are able to control (but not to cure) the disease, but they have to be started as soon as possible. There are other forms of amyloidosis (systemic or localized), for example systemic AA amyloidosis associated with chronic inflammatory diseases such as rheumatoid arthritis or localized cerebral Aß amyloidosis of the brain (Alzhaeimer's disease) and many others.
Protein electrophoresis is a laboratory method for the analysis of the proteins present in the body fluids. The sample of the serum (which is a “liquid” part of the whole blood, separated from the blood cells and the clotting factors) is placed on a gel and the electrical current is applied. The proteins then “run” on the gel, with the speed depending on their molecular mass (ie how big they are) and their electrical charge. The electrophoretic graph is then generated and the quantity of each group of proteins (such as albumin, globulins and immunoglobulins) can be estimated.