|Year : 2017 | Volume
| Issue : 6 | Page : 171-179
Mimics of scleroderma
Kaveri K Nalianda1, Mithun M Rathen2, Soumya Jagadeesan2, D Padmanabha Shenoy1
1 Centre for Arthritis and Rheumatism Excellence, Nettoor, India
2 Department of Dermatology, Amrita Institute of Medical Science, Kochi, Kerala, India
|Date of Web Publication||23-Nov-2017|
D Padmanabha Shenoy
Centre for Arthritis and Rheumatism Excellence, Nettoor, NH47, Kochi, Kerala - 682 040
Source of Support: None, Conflict of Interest: None
Systemic sclerosis is a rare autoimmune connective tissue disorder characterised typically by tightening and tethering of skin. However, several other disorders are also characterised by hardening and thickening of skin. These mimics can be potentially confused with systemic sclerosis, leading to a misdiagnosis. This review describes the aetiopathogenesis, clinical features and treatment of Morphea (localised scleroderma), Scleredema, Scleromyxoedema, Eosinophilic fasciitis, Nephrogenic Systemic Fibrosis, Diabetic Cheiroarthropathy, chronic GVHD, POEMS syndrome and drug induced scleroderma like illness. A careful and thorough clinical assessment is essential in order to differentiate these mimics from each other and from systemic sclerosis, establish the diagnosis, and initiate appropriate treatment.
Keywords: Eosinophilia myalgia syndrome, eosinophilic fasciitis, mimics, morphea, nephrogenic systemic fibrosis, scleredema, scleromyxedema, toxic oil syndrome
|How to cite this article:|
Nalianda KK, Rathen MM, Jagadeesan S, Shenoy D P. Mimics of scleroderma. Indian J Rheumatol 2017;12, Suppl S1:171-9
| Introduction|| |
Systemic sclerosis (SSc) or scleroderma is a rare autoimmune connective tissue disorder whose features include fibrosis of skin, obliterative vasculopathy, and autoimmunity.
The term scleroderma is derived from two Greek words “skleros” (hard) and “derma” (skin), which reflects the most prominent feature of this disease, the excessive deposition of collagen leading to fibrosis and tethering of skin. Hippocrates in his work “On Epidemics” has described treating a patient whose skin was so hard that “it was not possible to raise it in folds.” The clinical features are manifold due to the fibrosis of internal organs leading to multi-system involvement.
However, there are several other scleroderma-like disorders which are also characterized by hardening and thickening of skin as in SSc and can be potentially confused with SSc leading to a misdiagnosis.
The list of mimics of scleroderma is extensive. It can be subdivided into localized and systemic disorders. The systemic disorders can be further categorized as immune mediated, deposition, occupational, hereditary, metabolic, and toxin-induced disorders.
Circumscribed, linear, generalized, pansclerotic, mixed.
Inflammatory and immune-mediated - Eosinophilic fasciitis, Lichen sclerosus et atrophicus, Graft versus host disease, POEMS syndrome.
Deposition disorders-scleromyxedema, scleredema adultorum, nephrogenic systemic fibrosis, lipodermatosclerosis, systemic amyloidosis.
Metabolic - Hypothyroidism, Porphyria cutanea tarda, Phenylketonuria.
Hereditary: Congenital fascial dystrophy, Progeria, acrogeria, Werner 's syndrome.
Occupational exposure: Epoxy resins, Organic solvents, Polyvinyl chloride, Silica.
Toxin and chemical-induced:
- Drugs - Bisoprolol, bleomycin, bromocriptine, carbidopa, d-penicillamine, L-tryptophan, toxic oil syndrome
- Chemicals and Pesticides - Benzene naphthalene toluene trichloroethylene, malathion, diniconazole.
A careful and thorough clinical assessment is essential to differentiate these mimics from SSc and from each other. Features such as the distribution and quality of skin involvement, the presence of Raynaud's phenomenon, changes on nailfold capillaroscopy, associated concurrent disorders, and specific laboratory parameters can aid in establishing the diagnosis.
To confirm the clinical diagnosis, a full thickness skin-to-muscle biopsy is necessary in most cases. As some of these conditions can be effectively treated while others, portend a poor prognosis, it is essential to establish a definitive diagnosis and initiate appropriate treatment.
This article aims to discuss a few of these disorders mimicking scleroderma in greater detail.
| Morphea|| |
Morphea, also known as localized scleroderma, is an inflammatory disorder characterized by increased deposition of collagen in the skin and subcutaneous tissues leading to sclerosis. The absence of features such as Raynaud's phenomenon, sclerodactyly, nail bed capillary abnormalities and involvement of the internal organs differentiates localized from systemic scleroderma.
Morphea is a rare disorder with an incidence estimated to be between 0.34 and 2.7/100,000 population/annum. It can affect all races but most frequently affects whites. The prevalence of morphea is distributed equally between children and adults. While linear morphea is the most common variant in children, plaque or circumscribed morphea is the most common in adults.
Etiology and pathogenesis
Autoimmunity plays an important role in the pathogenesis of morphea. Similar to SSc, pathogenesis involves endothelial cells, fibroblasts, and inflammatory cells. Injury of vascular endothelium which could be due to trauma, infection (with Borrelia burgdorferi), hypoxia or radiation therapy could be an early event. This is followed by upregulation of expression of adhesion molecules and chemotactic cytokines and increased angiogenesis. Subsequently, there is recruitment of monocytes, macrophages, eosinophils, and CD4+ T cells and their infiltration of the reticular dermis of the skin. The endothelial and inflammatory cells release growth factors such as transforming growth factor beta 1, connective tissue growth factor, and cytokines such as IL-1, IL-4, IL-6, and IL-8 which lead to proliferation of fibroblast and increased collagen deposition.
A classification system was proposed by Peterson et al. in 1995 which categorized morphea into plaque morphea, generalized morphea, bullous, linear, and deep morphea. This classification was subsequently revised and morphea is now subdivided into five categories:
Generalized morpheaPansclerotic morpheaMixed morphea
(Source: Consensus Conference, Padua [Italy], 2004).
Mixed morphea was introduced as a new concept to describe patients who presented with a combination of two or more types of lesions.,,
Circumscribed morphea is also known as plaque morphea. In adults, it is the most common variant. The superficial form of circumscribed morphea is limited to the reticular dermis. Deep circumscribed morphea is characterized by fibrosis affecting the deep dermis, adipose tissue, and muscle but unlike the linear variety is not linear in the pattern but more diffuse.
Generally, the morphea lesions present as well-circumscribed areas of shiny indurated skin with a violaceous border (inflammatory stage). Lesions occur most frequently on trunk or limbs. Then, they undergo progressive induration and turn yellow or porcelain white. Hyperpigmentation, depigmentation, or atrophy may occur on the resolution. Erosions or blisters very occasionally may form over morphea plaques, giving rise to bullous morphea.
Also known as linear scleroderma, this is the most common variant of morphea or localized scleroderma in childhood comprising up to 65% of cases of juvenile morphea.
It appears usually as a single unilateral indurated lesion with a linear distribution. It occurs most commonly on scalp, face, and limbs. The induration extends to involve the dermis, subcutaneous tissue, muscle, and bone. In an extremity, when an induration crosses the joint line, it can lead to contractures. Arthritis can occur in 13% of patients with linear scleroderma.
En-coup-de sabre-A form of linear scleroderma is usually located on the scalp or face. The lesion presents classically as a unilateral, depressed, ivory-colored plaque on the paramedian forehead, reminiscent of a defect caused by a stroke of the sword.
Sometimes, lesions can extend onto or affect the cheek, nose, or upper lip exclusively.
Alopecia is present. In 15% of the patients, ocular complications such as xerophthalmia, episcleritis, uveitis, enophthalmos, eyelid lesions, and papilloedema can occur. En-coup-de-sabre can also be associated with neurological complications such as seizures, peripheral neuropathy, strokes, central nervous system (CNS) vasculitis, vascular malformations, or abnormalities on electroencephalography or magnetic resonance imaging.
Progressive facial hemiatrophy (or Parry Romberg Syndrome)-This is also another variant of linear morphea that causes hemiatrophy of the face by involving subcutaneous tissue, muscle, and bone. There is no sclerosis of the skin. Progressive facial hemiatrophy often coexists with lesions of typical morphea on the other parts of the body confirming that it is indeed a variant of linear scleroderma. It can result in significant deformity of the face and is associated with similar neurological complications as en-coup de sabre.
Generalized morphea is defined as the presence of multiple plaques in more than two anatomical areas or by the coalescence of individual plaques. The onset is usually insidious, and it can progress to involve extensive areas of the body. Up to 9% of these patients can have arthralgias. Unlike SSc, however, digital ulceration, nail fold capillary changes, Raynaud's phenomenon, resorption of phalanges, and internal organ involvement is very rare. Furthermore, the face is spared in generalized morphea.
This is a rare and aggressive variant of morphea which affects children typically. Besides the skin, it affects subcutaneous tissue, fascia, muscle, and bone. It starts off as plaques on the extensor surfaces of limbs and trunk, sparing fingertips and toes, and then progresses to full-thickness sclerosis of trunk, face, and extremities and can lead to painful ulceration, joint contractures, and calcifications.
Morphea is usually diagnosed based on the clinical features but often histopathological confirmation is required to exclude other disorders. In the early inflammatory phase, lymphocytes, macrophages, plasma cells, eosinophils, and mast cells are seen infiltrating the lesion and in the fibrotic phase, thickened, hyalinized collagen bundle extend to the superficial structures from the deep reticular dermis.
Laboratory abnormalities include eosinophilia, polyclonal hypergammaglobulinemia, elevated inflammatory markers, antinuclear antibodies (44%–80%), anti ssDNA antibodies (50%), and anti-histone antibodies (47%). Anti-centromere antibodies have been detected in 12% of patients with morphea, whereas anti-topoisomerase 1 antibodies have been reported only in a few cases. Anti-topoisomerase II alpha antibodies are found in up to 76% of patients of morphea compared to 14% of those with SSC.
Treatment efficacy is difficult to assess due to the lack of validated outcome measures. Thus, treatment is often challenging and must be based on the severity and extent of disease [Table 1].
The prognosis of morphea in terms of progression to systemic involvement is usually good. There is a tendency for lesions of morphea to spontaneously regress over 3–5 years with residual atrophic and pigmentary changes.
Emollients, topical, and systemic antipruritic agents can be used as symptomatic therapies. Physiotherapy can be of great benefit in patients with linear scleroderma to prevent contractures. Topical lubricants for plaque morphea include topical corticosteroids, topical tacrolimus, imiquimod 5% cream, vitamin D analogs, and UV radiation with or without 8-methoxypsoralen. A number of prospective and retrospective studies have demonstrated the efficacy of methotrexate (in doses of 0.3–0.4 mg/kg/week in children and between 15 and 25 mg/kg in adults) and systemic glucocorticoids in the treatment of morphea.
Mycophenolate mofetil has been found to be effective and well tolerated in children with morphea who have not responded to a combination of glucocorticoids and methotrexate. There have also been case reports of treatment with infliximab and imatinib leading to significant improvement in generalized morphea.
| Scleredema|| |
Scleredema adultorum of Buschke is a fibro mucinous connective tissue disorder whose etiology is unknown. It was first described in 1902 by Abraham Buschke, a German dermatologist. It is characterized by mucin and collagen deposition and occurs in the setting of three conditions: after certain infections, monoclonal gammopathies, and in association with poorly controlled diabetes.
Thus, scleredema adultorum is classified into three types as follows:
Type 1 which follows a febrile illness and resolves in several months and up to 2 years in most cases. It is the most prevalent type. Streptococcus, measles, mumps, influenza, and varicella are the pathogens associated. It is seen more commonly in females, usually affects individuals <20 years of age and can also affect children.
Type 2 is associated strongly with the development of paraproteinaemia including multiple myeloma. It is particularly associated with monoclonal gammopathy of the IgG kappa type.
It has a slow, chronic, and progressive course.
Type 3 occurs in patients with long-standing poorly controlled diabetes and is known as scleredema diabeticorum. Patients are generally over the age of 40, male and have microvascular complications of diabetes.
Scleredema, irrespective of subtype, is characterized by asymptomatic, woody, nonpitting induration of the skin, on the neck, upper back, shoulders, and arms. The indurated skin can have a peau d' orange appearance. Hands and feet are spared unlike SSc where sclerodactyly is universally present. Very rarely, systemic involvement characterized by cardiac dysfunction, esophageal dysfunction, and ocular palsy can occur.
Skin biopsy shows that the epidermis is not involved usually. The dermis can be thickened up to 4 times than a normal dermis. Collagen fibers are swollen and are separated by wide spaces filled with acid mucopolysaccharides.
Scleredema diagnosis is usually made clinically on the basis of extent of skin involvement and the nature of the associated conditions.
Patients with type 1 disease related to infection, develop symptoms rapidly within days to months after infection and resolve spontaneously within several months to 2 years. Type 2 is insidious in onset and is chronic and progressive. Type 3 is also slow in onset but could improve with better diabetic control.
In type 1, penicillin use in documented recent streptococcal infection has been suggested. UV light, radiation therapy, and immunosuppressants such as corticosteroids, methotrexate, and immunoglobulin (IVIg) have been advocated for use in the treatment of scleredema with varying degrees of therapeutic benefit.
| Scleromyxedema|| |
Scleromyxedema is a rare disorder affecting adults of middle age between 30 and 80 years. It is a cutaneous mucinosis and affects both genders equally. It is also known as generalized lichen myxedematosus and first described by Dubreuilh in 1906 though it was Gottron who coined the term scleromyxedema' in 1954.
The characteristic features are a generalized papular and sclerodermoid eruption, deposition of mucin, increased proliferation of fibroblasts and the presence of a monoclonal gammopathy in the absence of thyroid disease.
| Pathophysiology|| |
The etiology of this rare disorder is obscure. There is increased mucin deposition, fibroblast proliferation, and fibrosis. In patients with this disorder, fibroblasts produce a greater quantity of hyaluronic acid than normal fibroblasts and hence greater amounts of mucin as well. IgG paraproteinemia has been found to be present in 83% of patients with scleromyxedema, but isolated serum IgG does not cause excess proliferation of fibroblasts suggesting that there are nonparaprotein factors responsible. There are studies that have demonstrated that serum from patients can activate dermal fibroblasts to proliferate and produce hyaluronic acid and prostaglandins.
The hallmark is a symmetrical widespread eruption of small waxy, firm papules affecting face, neck, distal forearms, and hands but sparing palms, scalp, and mucous membranes.
The trunk can also be involved. Papules are often arranged in a linear fashion and are not pruritic. The skin has a characteristic texture described as “cobblestone.” Diffuse infiltration and mucin deposition in the face and particularly the glabella gives rise to a “leonine facies.” Deep furrowing can also be present on the shoulders and back (Shar-Pei sign). The proximal interphalangeal joints can be thickened and have raised borders with a central depression, referred to as the “doughnut sign.” There can be a loss of hair in eyebrows, groin, and axilla. Patients complain of the stiffness of hands, extremities and mouth. Scleromyxedema can have systemic manifestations.
The most common extracutaneous symptom is dysphagia. Involvement of larynx with decreased mobility of epiglottis and vocal cords can cause hoarseness of voice and aspiration. Myopathy has been known to occur which can present as a proximal or generalized weakness, usually months or years after the onset of skin lesions. There have been reports of a rheumatoid-like severe destructive polyarthritis in scleromyxedema.
In 10%–15% of patients with scleromyxedema, neurologic involvement is present in the form of carpal tunnel syndrome, peripheral neuropathy, headaches, dysarthria, and impaired cognition.
Dermato-neuro syndrome is a rare CNS manifestation characterized by high fevers, seizures, and coma often preceded by an influenza-like prodromal illness. Pulmonary involvement in the form of obstructive or restrictive lung disease, cardiac involvement in the form of atherosclerotic heart disease, acute myocardial infarction, heart block, and chronic renal disease have also been reported in patients with scleromyxedema.
The four typical criteria which have to be present to definitively diagnose this condition are:
- A generalized papular and sclerodermoid cutaneous eruption
- Skin biopsy with the classic histologic triad of mucin deposition, proliferation of fibroblasts and fibrosis
- A monoclonal gammopathy in the peripheral blood
- Absence of thyroid dysfunction.
The presence of papules is a key feature that helps in differentiating scleromyxedema clinically from morphea, SSc, and scleredema. Furthermore unlike in SSc, telangiectasias and calcinosis are absent in scleromyxedema. Nephrogenic systemic fibrosis (NSF) can be differentiated from scleromyxedema by the absence of facial involvement and paraproteinaemia.
The stiff hands in scleromyxedema can resemble the appearance of diabetic cheiroarthropathy superficially, but waxy papules are not seen in the latter condition.
Topical therapies such as UV light and corticosteroids have been found to have limited benefit. Therapeutic agents used for plasma cell dyscrasias such as melphalan, corticosteroids, cyclophosphamide, thalidomide, and bortezomib have been used. IVIg has been reported to produce a partial or even complete response in a few studies.,
| Eosinophilic Fasciitis|| |
Eosinophilic fasciitis (EF) is a very rare scleroderma-like disorder, first described by Schulman in 1974. Rodnan et al. later, coined the term eosinophilic fasciitis.
The prevalence and incidence of this rare disorder are not known. It is more common in men and predominant in Caucasians. It occurs between the third and sixth decade of life.
In the past, epidemics of the two conditions similar to EF have occurred due to consumption of toxic contaminants such as aniline denatured rapeseed oil (toxic oil syndrome in Spain, 1981) and L-tryptophan (eosinophilia-myalgia syndrome in the US, 1989). Both of these conditions had eosinophilia, fibrosis of the skin and pathological evidence of fasciitis. However, a more acute course associated with fever, extensive multisystem involvement and a high mortality rate differentiate these two disorders from EF. They are now considered to be mostly of historical significance as there have been no reports of new cases in the last few decades.
Etiology remains obscure. A few potential triggers have been considered. It has been reported to have an onset after vigorous exercise in about 50% of cases. No history of hereditary exposure leading to the onset of EF has been found. Borrelia burgdorferi i infection has been thought to play a role in the pathogenesis. In EF, the fibrosis rapidly develops as a result of an exaggerated immune response and a proinflammatory environment.
The classic histopathological feature of EF is inflammation and fibrosis of the fascia, and as the disease progresses, the fibrosis extends and involves the lower dermis and muscle. The involved tissue is infiltrated by mononuclear inflammatory cells and eosinophils. Local degranulation of these eosinophils causes the release of highly cationic granule proteins in the tissues which are toxic and fibrogenic.
The onset of EF is usually abrupt but can be subacute (over weeks to months) as well.,
In the early inflammatory phase, painful, tender, symmetrical induration of the subcutaneous tissues occurs involving forearms and calves and sometimes trunk and neck. Face and hands are spared in contrast to SSc.
The skin is edematous with a peau d' orange appearance. As the disease progresses, woody induration of the subcutaneous tissues occurs. The dermis gets tethered to the fascial and muscular layers leading to the puckering of skin and development of longitudinal furrowing or the “groove sign” on lifting the arms above the head. This represents the sparing of deep sclerosis in the area of the veins. Significantly, the fibrotic process does not affect the superficial layers of skin which can still be gently pinched into folds.,
A nonerosive symmetric arthritis is often seen. Severe flexion contractures may develop due to fibrosis of periarticular structures. Raynaud's phenomenon can be present, but nail fold capillaroscopy is normal.
While the aggressive disease can be associated with constitutional symptoms such as profound fatigue and loss of weight, there is usually no visceral involvement. Myeloproliferative disorders and leukemias can occur in <10% of patients.
The gold standard for diagnosis is considered to be a full thickness skin biopsy with the classical histopathological feature being the presence of dermal hypodermal sclerosis with fibrosis of subcutaneous adipose tissue, perimysium and sparing of the epidermis. Peripheral eosinophilia raised inflammatory markers and hypergammaglobulinemia are present. Fascial thickening can be picked up on T1, T2, and short tau inversion recovery imaging in the acute phases. Autoimmune serology is usually negative.
EF has been found to respond to corticosteroids. Doses of 0.5-1 mg/kg daily are initiated and maintained for a few weeks until a clinical response is seen. Following this, steroids may be tapered slowly with monitoring for relapse. It can take up to 12–18 months to obtain a full or satisfactory response.
Aggressive disease and the presence of significant constitutional symptoms often necessitate additional immunosuppressive therapy such as mycophenolate mofetil and methotrexate which have steroid-sparing effects.
Adjunctive physiotherapy is encouraged to decrease flexion contractures and resultant long-term disability. The aim of treatment ultimately is complete remission with a resolution of fibrotic manifestations; hence, the early implementation of early immunosuppressive therapy is important. The prognosis of EF is good with most patient achieving full remission and cure.
| Nephrogenic Systemic Fibrosis|| |
NSF was originally called nephrogenic fibrosing dermopathy and first described in 2000 by Cowper et al. who described scleromyxedema like skin lesions in 15 patients with end-stage renal disease undergoing dialysis. Extensive thickening and hardening of skin with brown hyperpigmentation, subcutaneous nodules, and papules were noted in these patients. Although the skin resembled scleromyxedema, the absence of systemic involvement and monoclonal paraproteinemia were indicative of a new and distinct clinical entity.
The nomenclature was changed to NSF in 2003 when systemic manifestations were recognized. Three years later in 2006, the development of NSF as a consequence of exposure to gadolinium-based contrast agent (GBCA) in patients with renal failure was reported.
It has been suggested that when patients with renal impairment are exposed to gadolinium contrast, the ionized form of gadolinium (GD3+) undergoes dissociation from its stable ligand complex to form insoluble molecules which ultimately precipitate in stroma and stimulate profibrotic cytokine production.
NSF usually occurs between 2 and 10 weeks after exposure to GD3+. Gadolinium deposits have been found in the involved skin. Patients are generally middle-aged and neither gender nor racial predilection has been reported. The USFDA in 2007, issued a black box warning against the use of GBCA in severe acute or chronic renal impairment.
Initially, there is an acute swelling of the distal parts of the extremities, with gradual enlarging papules and nodules that coalesce into plaques and over the following weeks, cutaneous thickening, induration, and hardening occurs. The trunk can also be involved but face is spared. Involvement can spread from the distal extremities to the elbows and knees. The fibrosis can extend from skin to muscle and fascia causing a deep, woody induration which can mimic eosinophilic fasciitis. It can cause painful joint contractures.,
Systemic involvement occurs due to fibrotic damage to the internal organs such as esophagus, lungs, heart, kidneys, and skeletal muscle. Raynaud's phenomenon is absent, and nail fold capillaroscopy is normal.,
A full thickness skin biopsy can help in diagnosis. Dermal fibrosis extending to subcutaneous fat septae is seen. CD34+ cells can be found in the dermis. Mucin and collagen along with CD34+ cells in the absence of monoclonal IgG paraprotein are considered to be highly characteristic of NSF and helps differentiate it from scleromyxedema.
Immunosuppressive agents such as prednisolone, cyclophosphamide and methotrexate have not been found to be very effective. Short-lived improvement in skin thickening, and tethering has been found with the tyrosine kinase inhibitor imatinib with relapse occurring on discontinuation of the drug. There have been case reports of renal transplantation leading to improvement in skin fibrosis. Pain management and physiotherapy are important conservative measures of management. Avoidance of GBCA or judicious use of these agents in renally impaired patients is essential to prevent the development of this disorder.,
| Diabetic Cheiroarthropathy|| |
Diabetic cheiroarthropathy is also known as limited joint mobility syndrome and is characterized by the thickened tight skin and joint contractures. It can be seen in both type 1 and type 2 diabetes patients. Up to 10%–50% of type 1 DM patients can be affected. Long-standing diabetes, poorly controlled blood sugars, and elevated hemoglobin A1c levels are the risk factors for developing this disorder. Excess of glucose leading to nonenzymatic glycosylation of collagen with fibroblast proliferation and excess production of matrix proteins leads to the development of diabetic cheiroarthropathy.
There is bilateral symmetrical induration and thickening of skin involving dorsum of hands and fingers which is termed “pseudoscleroderma.” Overtime, progressive finger joint contracture leads to an inability to fully oppose the fingers known as “prayer sign.” Involvement of the other joints of the upper and lower extremities can also occur. Diabetic cheiroarthropathy can be differentiated from SSc by the absence of Raynaud's, telangiectasias and normal nail fold capillaroscopy.
Thickening of the dermis, collagen accumulation with small amounts of mucin and sclerosis of the tendon sheath are visible on histology., Ultrasound and MRI can both reveal thickening of subcutaneous tissues and flexor tendon sheaths.
The aim of treatment is to halt the progression of the disease by the adequate control of blood glucose. Physiotherapy has also been recommended to reduce contractures and thereby physical disability.
| Chronic Graft Versus Host Disease|| |
Approximately 60% to 70% of patients who are recipients of an allogeneic stem cell or bone marrow transplant will develop chronic graft versus host disease (cGVHD) at some point. Although a multisystem disorder, skin is the most common organ affected. Damage of host organs including scleroderma-like skin changes occur due to reactions of the donor T lymphocytes against the organism of the recipient.
Thin white atrophic papules occur when the papillary dermis is involved whereas sclerotic plaques develop when there is involvement of the reticular dermis. Trunk and extremities can be involved. Contractures can occur and atrophy of the epidermis can lead to ulcerations in the legs and pretibial regions. Fat and subcutaneous tissue involvement can lead to a firm nodular texture.
cGVHD can also be associated with muscle weakness, cramping, pain, and mucosal involvement (dry mouth, ulcers). There can be involvement of any organ system in cGVHD.
cGVHD differs from SSc in that it involves the extremities and the trunk (rather than starting with the hands and is far more patchy in distribution than SSc. Raynaud's phenomenon is absent. cGVHD can sometimes be difficult to differentiate from localized scleroderma, but the involvement of the mucosa and the history of transplant is helpful.
Sclerotic GVHD can be treated with phototherapy. Systemic immunosuppressants such as systemic corticosteroids and mycophenolate have not been proven to be effective. Everolimus, sirolimus, and imatinib have shown efficacy in some studies.
POEMS syndrome is a rare neoplastic disorder affecting multiple organ systems and is associated with an underlying plasma cell dyscrasia.
POEMS is characterized by polyneuropathy, organomegaly, endocrinopathy, M protein (or monoclonal gammopathy), and skin changes.
Hyperpigmentation and thickening of the skin with sclerodermoid changes and limitation of joint movement are the cutaneous manifestations of POEMS syndrome.
Sclerotic bone lesions, Castleman's disease, papilloedema, ascites, pleural effusions, and thrombocytosis are the other important clinical features.
Histopathology of the sclerodermoid lesions shows nonspecific changes with an inflammatory infiltrate, hyperpigmentation of the basal layer and dermal fibrosis. Normal sweat glands and collagen help differentiate POEMS from SSc.
Control of the underlying plasma cell disorder is the basis of treatment.
| Drug-Induced Scleroderma-Like Illness|| |
There have been rare reports of the development of scleroderma-like disease as a consequence of administration of drugs such as pentazocine, interferon beta1 a, paclitaxel, methysergide, and gemcitabine. The skin changes vary in the extent of involvement and shape and are differentiated from SSc by the absence of involvement of internal organs and scleroderma-specific antibodies.
| Summary|| |
Several disorders, due to the presence of indurated skin and fibrosis can mimic SSc. Most of these mimics are rare and can be differentiated by a careful history, clinical examination, and often histopathology [Table 2]. Establishing a diagnosis will help in initiating appropriate therapy where indicated.
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[Table 1], [Table 2]