**5.1 Clinical feature**

*New Insights into Systemic Sclerosis*

**4.5 Differential diagnosis**

patient or one biopsy [34].

or reactivation of HPV [15, 37, 41].

be considered.

*infiltrates can be found.*

**Figure 15.**

**4.6 Treatment**

The differential diagnosis of extragenital lichen sclerosus includes morphea, vitiligo, tinea versicolor, anetoderma, or cutaneous lymphoma. In the case of genital lichen sclerosus, erosive lichen planus and erythroplasia of Queyrat must

*Skin biopsy of extragenital lichen sclerosus where atrophic thinned epidermis and mild vacuolar degeneration of the basal layer are present. In the superficial dermis, homogenized collagen with perivascular lymphocytic* 

Sometimes it is not possible to distinguish morphea from lichen because clinical and especially histopathological findings of both diseases can also be present in one

Topical medications, phototherapy, and systemic therapy have been used for the treatment of lichen sclerosus. The effect of topical corticosteroids was reported especially in genital lichen sclerosus, but mitigation has also been demonstrated in extragenital lichen. Effect of topical corticosteroid therapy has been reported in randomized treatment and retrospective studies. Phototherapy is preferred second-line treatment for patients with limited disease that cannot be effectively treated with topical corticosteroids. An alternative to topical corticosteroids is the use of calcineurin inhibitors pimecrolimus and tacrolimus despite concerns of possible increase of development of squamous cell carcinoma

The use of systemic therapy is limited to a small group of patients with progressive worsening of extragenital lichen sclerosus that failed to respond to a potent topical corticosteroid and phototherapy. For systemic therapy, methotrexate (15–20 mg/week) and systemic corticosteroids (1 g of intravenous methylpredniso-

lone sodium succinate for 3 consecutive days/month) can be used [42].

**100**

Initial clinical manifestation includes painful edema of the extremities, which progresses to fibrosis and pseudo-inflammatory appearance (**Figure 16**). The manifestation of the disease is typically symmetrical on extremities without involvement of the hands, feet, and face [43].

Laboratory findings include elevation of ESR, hypergammaglobulinemia and peripheral eosinophilia which can be present in the early phase of the disease. ANA titer and complement level are usually normal. Pancytopenia, anemia, thrombocytopenia, myeloproliferative disorders, and monoclonal gammopathy have been reported in association with eosinophilic fasciitis. The diagnosis of eosinophilic fasciitis is established via fascial biopsy and/or by MRI [44].

### **5.2 Histopathology**

Histologically eosinophils and mast cells are present, and dermal fibrosis with patchy infiltrates composed of lymphocytes and plasma cells are also present. In deep biopsy thickening of the fascia is typical, which may be 10–50 times the normal width [44].

### **5.3 Treatment**

Once the diagnosis of eosinophilic fasciitis is established via fascial biopsy and/ or MRI, prompt treatment is essential to preserve mobility and function and prevent joint contractures. Prompt therapy with oral corticosteroids (e.g., prednisone 1–2 mg/kg daily) is usually necessary for reduction or cessation of rapid disease progression and as prevention of mobility reduction and development of joint contractures. The response is typically noted within the first few weeks, and clinical improvement may be seen over several months. Alternatively, hydroxychloroquine, cyclosporine, dapsone, methotrexate, PUVA, or infliximab may be used alone or in combination with prednisone. Phototherapy as UVA1 can also be beneficial [45].

### **Figure 16.**

*Eosinophilic fasciitis with initial clinical manifestation of progressive fibrotic changes with pseudoinflammatory appearance.*

### **6. Nephrogenic systemic fibrosis**

Nephrogenic systemic fibrosis is most often observed in middle-aged adults but has also been described in children and elderly patients. There is no gender or race predilection. Renal dysfunction and exposure to gadolinium-based contrast medium play a crucial role in the pathogenesis. Although the context use of the gadolinium in a patient with renal dysfunction is irrefutable, the mechanisms of fibrosis are still unknown [46, 47].

### **6.1 Clinical features**

This disorder presents with large and thick, indurated plaques distributed symmetrically on the extremities and trunk. The skin lesions are irregular and erythematous with a tendency to develop hyperpigmentation. The manifestation on the extremities often results in joint contractures. The condition is frequently associated with considerable pain and loss of mobility. Extracutaneous manifestations include yellow scleral plaques and systemic fibrosis with involvement of the heart, lungs, and also skeletal muscles [48, 49].

### **6.2 Histopathology**

A deep biopsy is necessary for diagnosis. Histologic features include increased dermal fibroblast-like cells with positivity for CD34 and procollagen I. Haphazard arrangement of thickened collagen bundles is also present. Furthermore, vascular proliferation and mucin deposition may also be present.

### **6.3 Treatment**

Nephrogenic systemic fibrosis is refractory to treatment with corticosteroids and other immunosuppressive drugs. There have only been case reports of improvement with imatinib, rapamycin, phototherapy UVA1, PUVA, or plasmapheresis. Improvement in renal function after renal transplantation may improve this type of fibrosis [49].

### **7. Stiff skin syndrome**

This dysfunction may be hereditary as a congenital disorder or acquired during early childhood. Familiar hereditary subtype is caused by heterozygosity for a mutation in the gene that encodes fibrillin-1 (FBN1). Dysfunction of this gene results in the production of giant collagen fibrils in the affected fascia [50].

### **7.1 Clinical features**

Stiff skin syndrome is characterized by "rock hard" induration and thickening of the skin and subcutaneous tissues. Typical manifestation is on the buttocks and thighs with mild hypertrichosis without affecting the inguinal folds. This disorder does not affect the hands and feet. The condition is stable or slowly progressive, and abnormalities of internal organs are not typically observed. In differential diagnosis the disease may resemble scleredema, deep morphea, or linear scleroderma [51].

**103**

**Figure 17.**

*Systemic Sclerosis Mimics*

**7.2 Histopathology**

**7.3 Treatment**

**8. Scleromyxedema**

teinemia) [53].

**8.1 Pathogenesis**

**8.2 Clinical features**

*DOI: http://dx.doi.org/10.5772/intechopen.88546*

are mostly without any pathologies [52].

Histologically, significant thickness of fascia with deposition of hyaline without an associated inflammatory infiltrate can be found. Thickened collagen bundles and mucin deposition may be present in the dermis. The epidermis and papillary dermis

Treatment of stiff skin syndrome is very difficult, and no effective treatments have been reported. Physical therapy and regimen measures for the patient can help

Scleromyxedema is a chronic idiopathic disorder characterized by papules and lesion of induration with dermal mucin deposition and with an increase of dermal collagen resulting in skin sclerosis. Many patients with scleromyxedema have monoclonal gammopathy, with systemic or lethal manifestations. Scleromyxedema represents a generalized variant that needs to be distinguished from localized lichen myxedematosus (variant without sclerosis and parapro-

The exact pathogenesis of scleromyxedema is unknown, typically affecting middle-aged adults of both sexes equally. The role of the associated monoclonal gammopathy remains a matter of debate, because, for example, paraprotein levels do not correlate with progression of the disease. But clinical remission of scleromyxedema, during the reduction of paraprotein, that follows after autologous

In the clinical manifestation of scleromyxedema, typically widespread and sym-

metrically firm, waxy, and closely aligned papules are present (**Figure 17**).

to prevent progressive joint contractures and immobility [51, 52].

hematopoietic stem cell transplantation was described [53, 54].

*Scleromyxedema. Numerous skin-colored papules of the neck.*

### **7.2 Histopathology**

*New Insights into Systemic Sclerosis*

**6. Nephrogenic systemic fibrosis**

fibrosis are still unknown [46, 47].

heart, lungs, and also skeletal muscles [48, 49].

proliferation and mucin deposition may also be present.

**6.1 Clinical features**

**6.2 Histopathology**

**6.3 Treatment**

fibrosis [49].

**7. Stiff skin syndrome**

**7.1 Clinical features**

linear scleroderma [51].

Nephrogenic systemic fibrosis is most often observed in middle-aged adults but has also been described in children and elderly patients. There is no gender or race predilection. Renal dysfunction and exposure to gadolinium-based contrast medium play a crucial role in the pathogenesis. Although the context use of the gadolinium in a patient with renal dysfunction is irrefutable, the mechanisms of

This disorder presents with large and thick, indurated plaques distributed symmetrically on the extremities and trunk. The skin lesions are irregular and erythematous with a tendency to develop hyperpigmentation. The manifestation on the extremities often results in joint contractures. The condition is frequently associated with considerable pain and loss of mobility. Extracutaneous manifestations include yellow scleral plaques and systemic fibrosis with involvement of the

A deep biopsy is necessary for diagnosis. Histologic features include increased dermal fibroblast-like cells with positivity for CD34 and procollagen I. Haphazard arrangement of thickened collagen bundles is also present. Furthermore, vascular

Nephrogenic systemic fibrosis is refractory to treatment with corticosteroids and other immunosuppressive drugs. There have only been case reports of improvement with imatinib, rapamycin, phototherapy UVA1, PUVA, or plasmapheresis. Improvement in renal function after renal transplantation may improve this type of

This dysfunction may be hereditary as a congenital disorder or acquired during early childhood. Familiar hereditary subtype is caused by heterozygosity for a mutation in the gene that encodes fibrillin-1 (FBN1). Dysfunction of this gene results in the production of giant collagen fibrils in the affected fascia [50].

Stiff skin syndrome is characterized by "rock hard" induration and thickening of the skin and subcutaneous tissues. Typical manifestation is on the buttocks and thighs with mild hypertrichosis without affecting the inguinal folds. This disorder does not affect the hands and feet. The condition is stable or slowly progressive, and abnormalities of internal organs are not typically observed. In differential diagnosis the disease may resemble scleredema, deep morphea, or

**102**

Histologically, significant thickness of fascia with deposition of hyaline without an associated inflammatory infiltrate can be found. Thickened collagen bundles and mucin deposition may be present in the dermis. The epidermis and papillary dermis are mostly without any pathologies [52].

### **7.3 Treatment**

Treatment of stiff skin syndrome is very difficult, and no effective treatments have been reported. Physical therapy and regimen measures for the patient can help to prevent progressive joint contractures and immobility [51, 52].
