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Severe aplastic anemia associated with eosinophilic fasciitis: report of 4 cases and review of the literature.

de Masson A, Bouaziz JD, Peffault de Latour R, Benhamou Y, Moluçon-Chabrot C, Bay JO, Laquerrière A, Picquenot JM, Michonneau D, Leguy-Seguin V, Rybojad M, Bonnotte B, Jardin F, Lévesque H, Bagot M, Socié G - Medicine (Baltimore) (2013)

Bottom Line: It has been associated with hematologic disorders, such as aplastic anemia.Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case.Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%).

View Article: PubMed Central - PubMed

Affiliation: Université Paris Diderot, Sorbonne Paris Cité; AP-HP; Service de Dermatologie, Hôpital Saint Louis, Paris, France.

ABSTRACT
Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18-71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1).

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Patient 3. Redness, warmth, and woody induration of the skin of the left forearm (top). After 12 months of immunosuppressive therapy (bottom). Marked softening of the skin; veins have become visible. [This figure can be viewed in color online at http://www.md-journal.com].
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Figure 4: Patient 3. Redness, warmth, and woody induration of the skin of the left forearm (top). After 12 months of immunosuppressive therapy (bottom). Marked softening of the skin; veins have become visible. [This figure can be viewed in color online at http://www.md-journal.com].

Mentions: A 35-year-old bricklayer experienced a rapid onset (a few days) of painful swelling of the limbs, arthralgia, and myalgia. He reported no previous physical stress. A clinical examination revealed thickening of the skin and subcutaneous tissue involving the trunk and all 4 limbs, including the digits. Laboratory studies revealed eosinophilia (1.15 g/L), an elevated erythrocyte sedimentation rate (23 mm/h), and polyclonal hypergammaglobulinemia (20 g/L). The antinuclear antibody titer was <1:80, with no antibodies to extractable nuclear antigens, including anti-Scl70 and anticentromere antibodies. A leg fascial biopsy showed a mononuclear infiltration of lymphoplasmocytes and eosinophils involving the perimysial tissue and the fascia, confirming the diagnosis of diffuse EF. The epidermis was normal, whereas thickened collagen bundles were observed in the dermis as were straightening with parallel orientation of the elastic fibers. Daily treatment with 1 mg/kg prednisone was started. Eight months later, he experienced massive hematemesis and was admitted to the intensive care unit. An esophago-gastroduodenoscopy revealed a normal esophagus, hematin-covered gastric lesions and a gastric ulcer with an adherent clot. His full blood count showed aplastic anemia (hemoglobin 8.3 g/dL, reticulocytes 36 g/L), platelets 3 g/L, and leukocytes 1.8 g/L. A bone marrow biopsy confirmed the diagnosis of SAA. There was no PNH clone detected. After 9 months of prednisone therapy, his skin condition did not improve, and the patient required blood and platelet transfusions every 2 weeks. A clinical examination showed diffuse sclerosis of the skin and subcutaneous tissue, including sclerodactyly, affecting 90% of the total body surface area (Figure 4A). Venous furrowing (groove sign) was visible on the forearms, and the skin seemed dimpled with a peau d’orange appearance. The nipples, palms, and plantar surfaces were not affected. The edema and arthralgia resolved. A careful examination of the neck revealed patchy, ivory, atrophic lesions with a pigmented peripheral halo, indicative of guttate morphea. Raynaud phenomenon was present. Microhemorrhages, edema, giant capillaries, a decreased number of capillary loops and avascular areas were found on nail-fold capillaroscopy consistent with an organic microangiopathy. Neither gastroesophageal reflux nor renal failure was observed. Echocardiography revealed increased systolic pulmonary arterial pressure (41 mm Hg) with normal left ventricular function. The lung diffusion capacity for carbon monoxide was reduced (47% of the predictive value). High-resolution computed tomography of the chest was normal. The skin abnormalities gradually subsided (Figure 4B), but immunosuppressive therapy (2 courses of ATG plus CsA 5 mg/kg) failed to improve the aplasia after 24 months of follow-up. Unfortunately, no compatible donor was found for allogeneic hematopoietic stem cell transplantation (HSCT). The patient had severe Pseudomonas aeruginosa mastoiditis that required surgery and antibiotic treatment with partial sterilization; he then developed invasive pulmonary aspergillosis. He was still alive at the last follow-up.


Severe aplastic anemia associated with eosinophilic fasciitis: report of 4 cases and review of the literature.

de Masson A, Bouaziz JD, Peffault de Latour R, Benhamou Y, Moluçon-Chabrot C, Bay JO, Laquerrière A, Picquenot JM, Michonneau D, Leguy-Seguin V, Rybojad M, Bonnotte B, Jardin F, Lévesque H, Bagot M, Socié G - Medicine (Baltimore) (2013)

Patient 3. Redness, warmth, and woody induration of the skin of the left forearm (top). After 12 months of immunosuppressive therapy (bottom). Marked softening of the skin; veins have become visible. [This figure can be viewed in color online at http://www.md-journal.com].
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4553982&req=5

Figure 4: Patient 3. Redness, warmth, and woody induration of the skin of the left forearm (top). After 12 months of immunosuppressive therapy (bottom). Marked softening of the skin; veins have become visible. [This figure can be viewed in color online at http://www.md-journal.com].
Mentions: A 35-year-old bricklayer experienced a rapid onset (a few days) of painful swelling of the limbs, arthralgia, and myalgia. He reported no previous physical stress. A clinical examination revealed thickening of the skin and subcutaneous tissue involving the trunk and all 4 limbs, including the digits. Laboratory studies revealed eosinophilia (1.15 g/L), an elevated erythrocyte sedimentation rate (23 mm/h), and polyclonal hypergammaglobulinemia (20 g/L). The antinuclear antibody titer was <1:80, with no antibodies to extractable nuclear antigens, including anti-Scl70 and anticentromere antibodies. A leg fascial biopsy showed a mononuclear infiltration of lymphoplasmocytes and eosinophils involving the perimysial tissue and the fascia, confirming the diagnosis of diffuse EF. The epidermis was normal, whereas thickened collagen bundles were observed in the dermis as were straightening with parallel orientation of the elastic fibers. Daily treatment with 1 mg/kg prednisone was started. Eight months later, he experienced massive hematemesis and was admitted to the intensive care unit. An esophago-gastroduodenoscopy revealed a normal esophagus, hematin-covered gastric lesions and a gastric ulcer with an adherent clot. His full blood count showed aplastic anemia (hemoglobin 8.3 g/dL, reticulocytes 36 g/L), platelets 3 g/L, and leukocytes 1.8 g/L. A bone marrow biopsy confirmed the diagnosis of SAA. There was no PNH clone detected. After 9 months of prednisone therapy, his skin condition did not improve, and the patient required blood and platelet transfusions every 2 weeks. A clinical examination showed diffuse sclerosis of the skin and subcutaneous tissue, including sclerodactyly, affecting 90% of the total body surface area (Figure 4A). Venous furrowing (groove sign) was visible on the forearms, and the skin seemed dimpled with a peau d’orange appearance. The nipples, palms, and plantar surfaces were not affected. The edema and arthralgia resolved. A careful examination of the neck revealed patchy, ivory, atrophic lesions with a pigmented peripheral halo, indicative of guttate morphea. Raynaud phenomenon was present. Microhemorrhages, edema, giant capillaries, a decreased number of capillary loops and avascular areas were found on nail-fold capillaroscopy consistent with an organic microangiopathy. Neither gastroesophageal reflux nor renal failure was observed. Echocardiography revealed increased systolic pulmonary arterial pressure (41 mm Hg) with normal left ventricular function. The lung diffusion capacity for carbon monoxide was reduced (47% of the predictive value). High-resolution computed tomography of the chest was normal. The skin abnormalities gradually subsided (Figure 4B), but immunosuppressive therapy (2 courses of ATG plus CsA 5 mg/kg) failed to improve the aplasia after 24 months of follow-up. Unfortunately, no compatible donor was found for allogeneic hematopoietic stem cell transplantation (HSCT). The patient had severe Pseudomonas aeruginosa mastoiditis that required surgery and antibiotic treatment with partial sterilization; he then developed invasive pulmonary aspergillosis. He was still alive at the last follow-up.

Bottom Line: It has been associated with hematologic disorders, such as aplastic anemia.Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case.Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%).

View Article: PubMed Central - PubMed

Affiliation: Université Paris Diderot, Sorbonne Paris Cité; AP-HP; Service de Dermatologie, Hôpital Saint Louis, Paris, France.

ABSTRACT
Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18-71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1).

Show MeSH
Related in: MedlinePlus