Sir, Eosinophilic fasciitis (EF) is a rare connective-tissue disorder clinically characterized by symmetrical and painful swelling associated to progressive induration and thickening of both skin and soft tissues, especially on the extremities. In contrast to other connective-tissue diseases, Raynaud’s phenomenon, sclerodactily, and abnormal nailfold capillaroscope readings are usually absent as antinuclear antibody and extractable nuclear antigen. Furthermore, peripheral eosinophilia, hypergammaglobulinemia, and a high erythrocyte sedimentation rate can be found. Despite the absence of a consensus on EF diagnostic criteria, the association of both clinical and histological characteristics (ie, fascia thickening intermingled with an eosinophilic infiltrate) leads to the diagnosis. EF therapy has not yet been standardized. However, besides systemic steroids, currently considered as the elective treatment,1 immunosuppressive drugs (such as cyclosporine and methotrexate) are successfully administered to nonresponder patients.2 Moreover, both PUVA (psoralen combined with ultraviolet A) and extracorporeal photopheresis (ECP) have been reported in recalcitrant cases.3 Herein, we describe a EF case treated with ECP and bosentan. A 50-year-old man presented with 1-year history of eosinophilia, malaise, arthromyalgia, and erythematous, edematous plaques (Figure 1) on the lower limbs. On the same areas, he complained of stiffness and swelling, as well. At blood examination, a slight eosinophilia 0.71 103 /mm3 (9.8%) and lymphocyte percentage decrease (11.3%) were observed. In addition, positivity for antinuclear antibodies (1:1280) was found. To rule out hematological disorders, bone marrow biopsy and chest and abdomen computed tomography scan were performed with no sign of an internal disease. A biopsy on the leg revealed normal epidermis, edema in the medium and deep dermis, and muscular fascia thickened with an infiltrate of plasma cells (Figure 2). Despite the absence of the muscular component in the biopsy, the clinical–pathological correlation suggested EF diagnosis. Moreover, nail-fold capillaroscope readings were negative. Oral methylprednisolone (0.5 mg/kg/d) was administered in association with PUVA therapy (4 times a week). Two months afterward, 2 small (<0.5 cm) nummular and painful ulcers were observed on the left leg and hydrocolloid plaques were applied. Four months after the start of therapy, no improvement was observed, so PUVA therapy and oral steroids were stopped. ECP was started, scheduled in 1 cycle (on 2 consecutive days at 2-week intervals for 3 months, thereafter scheduled every 4 weeks for 10 months). The disease improved slightly after 4 cycles. However, the 2 ulcers did not improve. Bosentan therapy was administered (125 mg/d, increased 1 month later to 250 mg/d). Three months afterward, the stiffness had subsided, the plaques turned brownish, and ulcers appeared smaller. Twelve months from the start of both ECP and bosentan treatment, neither EF nor ulcers were observed. Bosentan was tapered within a few weeks. After 13 months, ECP was stopped. Even if sporadic EF cases with spontaneous regression have been described, most of the patients require systemic therapies. Most patients have been successfully treated with steroids.1 However, recalcitrant cases can also be managed with methotrexate,2 cyclosporine, cyclophosphamide, azathioprine, and pennicillamine. ECP is a well-known therapy in cutaneous T-cell lymphoma, transplant rejection, graftversus-host disease, progressive multiple sclerosis, and severe atopic dermatitis.4-7 However, only Romano et al3 have reported 3 EF cases successfully treated with ECP. Unlike our case, ECP was managed on 2 consecutive day cycles at 2-week intervals for the first 3 months and thereafter every 4 weeks. It is thought that ECP could play a role in the immunomodulatory response by increasing interleukin-1 (IL-1), IL-6, IL-12, interferon-α, and interferon-γ levels. This provides a rationale for the treatment of recalcitrant EF cases. In accordance with Romano et al,3 we administered ECP after the immunosuppressant drugs (ie, methylprednisolone) as second-line therapy. Interestingly, our patient started bosentan as ulcer treatment. Bosentan, a dual endothelin-1 receptor antagonist, is effective in systemic sclerosis both as pulmonary hypertension management and as digital ulcer prevention.8 However, recent articles have reported bosentan’s effectiveness as digital ulcers treatment in systemic sclerosis.9,10 In our case, it is noteworthy that there was a clear-cut improvement after bosentan was started. We, for the first time, have associated ECP and bosentan in EF treatment. Based on our experience, we can question whether ECP and bosentan, by playing on different metabolic pathways, might have a synergistic action in EF or is it only a fortuitous coincidence

Bosentan and Extracorporeal Photochemotherapy in Eosinophilic Fasciitis: Synergistic Action or Fortuitous Coincidence?

PILERI, ALESSANDRO;PATRIZI, ANNALISA;BARDAZZI, FEDERICO
2014

Abstract

Sir, Eosinophilic fasciitis (EF) is a rare connective-tissue disorder clinically characterized by symmetrical and painful swelling associated to progressive induration and thickening of both skin and soft tissues, especially on the extremities. In contrast to other connective-tissue diseases, Raynaud’s phenomenon, sclerodactily, and abnormal nailfold capillaroscope readings are usually absent as antinuclear antibody and extractable nuclear antigen. Furthermore, peripheral eosinophilia, hypergammaglobulinemia, and a high erythrocyte sedimentation rate can be found. Despite the absence of a consensus on EF diagnostic criteria, the association of both clinical and histological characteristics (ie, fascia thickening intermingled with an eosinophilic infiltrate) leads to the diagnosis. EF therapy has not yet been standardized. However, besides systemic steroids, currently considered as the elective treatment,1 immunosuppressive drugs (such as cyclosporine and methotrexate) are successfully administered to nonresponder patients.2 Moreover, both PUVA (psoralen combined with ultraviolet A) and extracorporeal photopheresis (ECP) have been reported in recalcitrant cases.3 Herein, we describe a EF case treated with ECP and bosentan. A 50-year-old man presented with 1-year history of eosinophilia, malaise, arthromyalgia, and erythematous, edematous plaques (Figure 1) on the lower limbs. On the same areas, he complained of stiffness and swelling, as well. At blood examination, a slight eosinophilia 0.71 103 /mm3 (9.8%) and lymphocyte percentage decrease (11.3%) were observed. In addition, positivity for antinuclear antibodies (1:1280) was found. To rule out hematological disorders, bone marrow biopsy and chest and abdomen computed tomography scan were performed with no sign of an internal disease. A biopsy on the leg revealed normal epidermis, edema in the medium and deep dermis, and muscular fascia thickened with an infiltrate of plasma cells (Figure 2). Despite the absence of the muscular component in the biopsy, the clinical–pathological correlation suggested EF diagnosis. Moreover, nail-fold capillaroscope readings were negative. Oral methylprednisolone (0.5 mg/kg/d) was administered in association with PUVA therapy (4 times a week). Two months afterward, 2 small (<0.5 cm) nummular and painful ulcers were observed on the left leg and hydrocolloid plaques were applied. Four months after the start of therapy, no improvement was observed, so PUVA therapy and oral steroids were stopped. ECP was started, scheduled in 1 cycle (on 2 consecutive days at 2-week intervals for 3 months, thereafter scheduled every 4 weeks for 10 months). The disease improved slightly after 4 cycles. However, the 2 ulcers did not improve. Bosentan therapy was administered (125 mg/d, increased 1 month later to 250 mg/d). Three months afterward, the stiffness had subsided, the plaques turned brownish, and ulcers appeared smaller. Twelve months from the start of both ECP and bosentan treatment, neither EF nor ulcers were observed. Bosentan was tapered within a few weeks. After 13 months, ECP was stopped. Even if sporadic EF cases with spontaneous regression have been described, most of the patients require systemic therapies. Most patients have been successfully treated with steroids.1 However, recalcitrant cases can also be managed with methotrexate,2 cyclosporine, cyclophosphamide, azathioprine, and pennicillamine. ECP is a well-known therapy in cutaneous T-cell lymphoma, transplant rejection, graftversus-host disease, progressive multiple sclerosis, and severe atopic dermatitis.4-7 However, only Romano et al3 have reported 3 EF cases successfully treated with ECP. Unlike our case, ECP was managed on 2 consecutive day cycles at 2-week intervals for the first 3 months and thereafter every 4 weeks. It is thought that ECP could play a role in the immunomodulatory response by increasing interleukin-1 (IL-1), IL-6, IL-12, interferon-α, and interferon-γ levels. This provides a rationale for the treatment of recalcitrant EF cases. In accordance with Romano et al,3 we administered ECP after the immunosuppressant drugs (ie, methylprednisolone) as second-line therapy. Interestingly, our patient started bosentan as ulcer treatment. Bosentan, a dual endothelin-1 receptor antagonist, is effective in systemic sclerosis both as pulmonary hypertension management and as digital ulcer prevention.8 However, recent articles have reported bosentan’s effectiveness as digital ulcers treatment in systemic sclerosis.9,10 In our case, it is noteworthy that there was a clear-cut improvement after bosentan was started. We, for the first time, have associated ECP and bosentan in EF treatment. Based on our experience, we can question whether ECP and bosentan, by playing on different metabolic pathways, might have a synergistic action in EF or is it only a fortuitous coincidence
2014
Pileri A; Odorici G; Giudice V; Patrizi A; Bardazzi F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/388293
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