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Atypical Linear IgA Dermatosis Revealing Angioimmunoblastic T-Cell Lymphoma

Atypical Linear IgA Dermatosis Revealing Angioimmunoblastic T-Cell Lymphoma Angioimmunoblastic T-cell lymphoma (AITL) is frequently accompanied by dermatologic and autoimmune manifestations. We report an unusual case of AITL associated with atypical linear IgA bullous dermatosis (LAD). Report of a Case A 47-year-old man with a history of epilepsy treated for many years with sodium valproate, gabapentin, and clonazepam developed generalized pruritus, night sweats, and urticarialike lesions 2 weeks after the introduction of citalopram to his drug regimen. These symptoms were first interpreted to indicate a drug reaction, but they did not resolve after the discontinuation of the new antidepressant and antihistamine therapy. Three months later, he showed low-grade fever, weight loss, and peripheral lymphadenopathy. A pale erythematous eruption on the upper body and large violaceous plaques with large bullae on the hands, feet (Figure 1), elbows, and knees resolved spontaneously. Nikolsky sign was negative. Mucosal examination findings were normal. Figure 1 View LargeDownload Violaceous erythema and bullae of the foot. The results of laboratory tests showed lymphocytosis (lymphocyte count, 8500/μL) with large atypical lymphocytes and abnormal phenotype, hypereosinophilia (eosinophil count, 2900/μL), macrocytic anemia (hemoglobin level, 0.68 g/dL), elevated β2-microglobulin levels (0.0031 mg/L), and polyclonalhyper-γ-globulinemia (IgG level, 3600 mg/dL; IgA level, 2000 mg/dL). Anti–smooth muscle antibody titer was positive (1/320). Skin biopsy specimens showed subepidermal blistering with perivascular lymphocytic infiltrate in the dermis, mostly CD3+, CD5+, CD7−, and CD10− T cells with scattered CXCL13+ lymphocytes (Figure 2A and B). (To convert lymphocytes and eosinophils to number of cells × 109/L, multiply by 0.001; to convert hemoglobin to grams per liter, multiply by 10; to convert IgG to grams per liter, multiply by 0.01; to convert IgA to milligrams per liter, multiply by 10.) Figure 2 View LargeDownload Histopathologic (A), immunohistochemical (B), and direct immunofluorescence (C) images from the present case. A, Subepidermal blister with secondary necrotic changes of the epidermis; in the blister floor, regenerative epidermis overlays a mild dermal lymphocytic perivascular infiltrate (hematoxylin-eosin, original magnification ×100). B, Few scattered CXCL13+ lymphocytes are present within the dermal infiltrates (arrows) (original magnification ×200). C, The basement membrane zone shows a linear pattern of staining for C3 (original magnification ×200). Direct immunofluorescence showed a strong linear IgA deposit and weak IgG and C3 deposits at the basement membrane zone (Figure 2C). Findings of indirect immunofluorescence were negative on normal and salt-split human skin as were the findings of serum enzyme-linked immunosorbent assay immunoblot reactivity using anti-IgA and anti-IgG antibodies against dermal and epidermal extracts. Cervical lymph node biopsy findings were consistent with AITL. An identical dominant T-cell clone was detected in blood, skin, and lymph node samples. Findings of in situ hybridization for Epstein-Barr virus (Epstein-Barr virus–encoded RNAs) were negative in the skin and positive in the lymph nodes. Although bullous pemphigoid could not be completely ruled out, the diagnosis was atypical LAD. The patient received treatment with 4 cycles of rituximab-CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone) and showed partial resolution of the disease within the lymph nodes. However, cutaneous manifestations did not recur. Comment In nearly half of cases, AITL is accompanied by nonspecific dermatologic manifestations,1 often a maculopapular eruption mimicking viral exanthema or a drug reaction. These signs are frequently reported after drug intake and resolve spontaneously. Infiltrated lesions suggestive of cutaneous T-cell lymphoma are seen less frequently.2 In our patient, a reaction to citalopram was possible, but the disease continued to progress 3 months after discontinuation of citalopram treatment. In addition, the lymphadenopathy and large atypical blood cells led to the diagnosis of AITL. Histologic findings are often subtle, showing mild lymphocytic infiltrate around skin appendages and dermal vessels.2 Therefore, findings on molecular analysis of T-cell receptor gene rearrangement and on skin biopsy specimens of CXCL13 expression help establish the correct diagnosis.2,3 Classic cases of AITL include findings of clonal and oligoclonal B-cell proliferations, hyper-γ-globulinemia,4 autoimmune manifestations, and autoantibodies.2 In our patient, AITL may have promoted the development of an autoreactive B-cell clone, producing anti–basement membrane zone antibodies. Interestingly, neoplastic T cells were present in the skin at the sites of blistering, and no circulating antibodies against skin antigens were found. While an association between AITL and bullous dermatosis is extremely rare, this is the second documented case to our knowledge of LAD associated with AITL.5 Back to top Article Information Correspondence: Dr Bagot, Hôpital Henri Mondor, 51 Avenue du Maréchal de-Lattre-de-Tassigny, 94010, Créteil, France (martine.bagot@hmn.aphp.fr). Financial Disclosure: None reported. References 1. Dogan AAttygalle ADKyriakou C Angioimmunoblastic T-cell lymphoma. Br J Haematol 2003;121 (5) 681- 691PubMedGoogle ScholarCrossref 2. Martel PLaroche LCourville PFrench Study Group on Cutaneous Lymphomas, Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia: a clinical, immunohistological, and molecular analysis. Arch Dermatol 2000;136 (7) 881- 886PubMedGoogle ScholarCrossref 3. Ortonne NDupuis JPlonquet A Characterization of CXCL13+ neoplastic T cells in cutaneous lesions of angioimmunoblastic T-cell lymphoma (AITL). Am J Surg Pathol 2007;31 (7) 1068- 1076PubMedGoogle ScholarCrossref 4. Willenbrock KBräuninger AHansmann ML Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein-Barr virus-infected cells in early cases. Br J Haematol 2007;138 (6) 733- 739PubMedGoogle ScholarCrossref 5. Harms MSaurat JH Angioimmunoblastic lymphadenopathy accompanied by Duhring disease-like lesions. Hautarzt 1995;46 (11) 813PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Atypical Linear IgA Dermatosis Revealing Angioimmunoblastic T-Cell Lymphoma

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Publisher
American Medical Association
Copyright
Copyright © 2009 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archdermatol.2008.607
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Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is frequently accompanied by dermatologic and autoimmune manifestations. We report an unusual case of AITL associated with atypical linear IgA bullous dermatosis (LAD). Report of a Case A 47-year-old man with a history of epilepsy treated for many years with sodium valproate, gabapentin, and clonazepam developed generalized pruritus, night sweats, and urticarialike lesions 2 weeks after the introduction of citalopram to his drug regimen. These symptoms were first interpreted to indicate a drug reaction, but they did not resolve after the discontinuation of the new antidepressant and antihistamine therapy. Three months later, he showed low-grade fever, weight loss, and peripheral lymphadenopathy. A pale erythematous eruption on the upper body and large violaceous plaques with large bullae on the hands, feet (Figure 1), elbows, and knees resolved spontaneously. Nikolsky sign was negative. Mucosal examination findings were normal. Figure 1 View LargeDownload Violaceous erythema and bullae of the foot. The results of laboratory tests showed lymphocytosis (lymphocyte count, 8500/μL) with large atypical lymphocytes and abnormal phenotype, hypereosinophilia (eosinophil count, 2900/μL), macrocytic anemia (hemoglobin level, 0.68 g/dL), elevated β2-microglobulin levels (0.0031 mg/L), and polyclonalhyper-γ-globulinemia (IgG level, 3600 mg/dL; IgA level, 2000 mg/dL). Anti–smooth muscle antibody titer was positive (1/320). Skin biopsy specimens showed subepidermal blistering with perivascular lymphocytic infiltrate in the dermis, mostly CD3+, CD5+, CD7−, and CD10− T cells with scattered CXCL13+ lymphocytes (Figure 2A and B). (To convert lymphocytes and eosinophils to number of cells × 109/L, multiply by 0.001; to convert hemoglobin to grams per liter, multiply by 10; to convert IgG to grams per liter, multiply by 0.01; to convert IgA to milligrams per liter, multiply by 10.) Figure 2 View LargeDownload Histopathologic (A), immunohistochemical (B), and direct immunofluorescence (C) images from the present case. A, Subepidermal blister with secondary necrotic changes of the epidermis; in the blister floor, regenerative epidermis overlays a mild dermal lymphocytic perivascular infiltrate (hematoxylin-eosin, original magnification ×100). B, Few scattered CXCL13+ lymphocytes are present within the dermal infiltrates (arrows) (original magnification ×200). C, The basement membrane zone shows a linear pattern of staining for C3 (original magnification ×200). Direct immunofluorescence showed a strong linear IgA deposit and weak IgG and C3 deposits at the basement membrane zone (Figure 2C). Findings of indirect immunofluorescence were negative on normal and salt-split human skin as were the findings of serum enzyme-linked immunosorbent assay immunoblot reactivity using anti-IgA and anti-IgG antibodies against dermal and epidermal extracts. Cervical lymph node biopsy findings were consistent with AITL. An identical dominant T-cell clone was detected in blood, skin, and lymph node samples. Findings of in situ hybridization for Epstein-Barr virus (Epstein-Barr virus–encoded RNAs) were negative in the skin and positive in the lymph nodes. Although bullous pemphigoid could not be completely ruled out, the diagnosis was atypical LAD. The patient received treatment with 4 cycles of rituximab-CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone) and showed partial resolution of the disease within the lymph nodes. However, cutaneous manifestations did not recur. Comment In nearly half of cases, AITL is accompanied by nonspecific dermatologic manifestations,1 often a maculopapular eruption mimicking viral exanthema or a drug reaction. These signs are frequently reported after drug intake and resolve spontaneously. Infiltrated lesions suggestive of cutaneous T-cell lymphoma are seen less frequently.2 In our patient, a reaction to citalopram was possible, but the disease continued to progress 3 months after discontinuation of citalopram treatment. In addition, the lymphadenopathy and large atypical blood cells led to the diagnosis of AITL. Histologic findings are often subtle, showing mild lymphocytic infiltrate around skin appendages and dermal vessels.2 Therefore, findings on molecular analysis of T-cell receptor gene rearrangement and on skin biopsy specimens of CXCL13 expression help establish the correct diagnosis.2,3 Classic cases of AITL include findings of clonal and oligoclonal B-cell proliferations, hyper-γ-globulinemia,4 autoimmune manifestations, and autoantibodies.2 In our patient, AITL may have promoted the development of an autoreactive B-cell clone, producing anti–basement membrane zone antibodies. Interestingly, neoplastic T cells were present in the skin at the sites of blistering, and no circulating antibodies against skin antigens were found. While an association between AITL and bullous dermatosis is extremely rare, this is the second documented case to our knowledge of LAD associated with AITL.5 Back to top Article Information Correspondence: Dr Bagot, Hôpital Henri Mondor, 51 Avenue du Maréchal de-Lattre-de-Tassigny, 94010, Créteil, France (martine.bagot@hmn.aphp.fr). Financial Disclosure: None reported. References 1. Dogan AAttygalle ADKyriakou C Angioimmunoblastic T-cell lymphoma. Br J Haematol 2003;121 (5) 681- 691PubMedGoogle ScholarCrossref 2. Martel PLaroche LCourville PFrench Study Group on Cutaneous Lymphomas, Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia: a clinical, immunohistological, and molecular analysis. Arch Dermatol 2000;136 (7) 881- 886PubMedGoogle ScholarCrossref 3. Ortonne NDupuis JPlonquet A Characterization of CXCL13+ neoplastic T cells in cutaneous lesions of angioimmunoblastic T-cell lymphoma (AITL). Am J Surg Pathol 2007;31 (7) 1068- 1076PubMedGoogle ScholarCrossref 4. Willenbrock KBräuninger AHansmann ML Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein-Barr virus-infected cells in early cases. Br J Haematol 2007;138 (6) 733- 739PubMedGoogle ScholarCrossref 5. Harms MSaurat JH Angioimmunoblastic lymphadenopathy accompanied by Duhring disease-like lesions. Hautarzt 1995;46 (11) 813PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Mar 1, 2009

Keywords: angioimmunoblastic lymphadenopathy,linear iga dermatosis

References