A review of rituximab in cutaneous medicine
Noah Scheinfeld
Dermatology Online Journal 12 (1): 3

Department of Dermatology St. Lukes Roosevelt Hospital Center, New York, NY. Scheinfeld@earthlink.net

Abstract

The rituximab antibody is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Rituximab is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. Rituximab is also commonly used to treat chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, and immune or idiopathic thrombocytopenic purpura (ITP). Rituximab is an effective treatment for primary cutaneous B-cell lymphoma and other cutaneous lymphomas. Rituximab is an effective treatment for mixed cryoglobulinemia. Rituximab is a promising treatment for systemic lupus erythematosus, dermatomyositis, pemphigus, vasculitis, and a variety of hematologic diseases. Black-box warnings on rituximab include fatal infusion reactions, tumor lysis syndrome, and severe mucocutaneous reactions. A variety of cardiac, pulmonary, renal, and hematologic side effects can occur. It commonly causes mild cutaneous side effect and rarely has caused paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.



Introduction

Rituximab is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma [1]. Rituximab is also commonly used to treat chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, and immune or idiopathic thrombocytopenic purpura (ITP). It is a promising agent for the treatment on any disease called by B-Cells and the pathogenic antibodies that they produce [1].


Pharmacology

The rituximab antibody is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1-κ immunoglobulin containing murine light-chain and heavy-chain variable region sequences and human constant region sequences. Rituximab is composed of two heavy chains of 451 amino acids and two light chains of 213 amino acids (based on cDNA analysis) and has an approximate molecular weight of 145 kD. Rituximab has a binding affinity for the CD20 antigen of approximately 8.0 nM [1].

Rituximab binds specifically to the antigen CD20 (human B lymphocyte restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre- and mature-B lymphocytes. The antigen is also expressed on > 90 percent of B-cell non Hodgkin lymphomas (NHL), but is not found on hematopoietic stem cells, pro-B cells, normal plasma cells, or other normal tissues. CD20 regulates early steps in the activation process for cell-cycle initiation and differentiation, and possibly functions as a calcium ion channel. CD20 is not shed from the cell surface and does not internalize upon antibody binding. Free CD20 antigen is not found in the circulation [1].

The Fab domain of Rituximab binds to the CD20 antigen on B lymphocytes, and the Fc domain recruits immune effector functions to mediate B-cell lysis in vitro. Possible mechanisms of cell lysis include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The antibody has been shown to induce apoptosis in the DHL-4 human B-cell lymphoma line. Rituximab binding has been observed on lymphoid cells in the thymus, the white pulp of the spleen, and a majority of B lymphocytes in peripheral blood and lymph nodes. Little or no binding was observed in the nonlymphoid tissues examined [1].

Rituximab is usually given in a dose of 375 mg intravenously once a week for 4-8 weeks, often with other types of chemotherapy. Therapy using rituximab often utilizes combinations such as CHOP or fludarabine and cyclophosphamide. Rituximab is sometimes administered with ibritumomab tiuxetan.


Uses of rituximab to treat diseases with cutaneous manifestations


Treatment of cutaneous B cell lymphoma

Rituximab is an effective treatment for primary cutaneous B-cell lymphomas [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]. This is even true in cases of primary cutaneous B-cell lymphoma that have relapsed or failed other therapies [13].

Rituximab is an effective therapy of atypical B-cell-lymphoma variants. Primary cutaneous large B-cell lymphoma mimicking pyoderma gangrenosum of the leg has been effectively treated with rituximab [14, 15, 16, 17]. Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer can be treated with rituximab [18]. Systemic therapy of primary cutaneous B-cell lymphoma, marginal-zone type, with rituximab, has been successful [19]. Regression of cutaneous intravascular lymphoma with rituximab has been noted [20].

Intralesional therapy with anti-CD20 monoclonal antibody rituximab has been found to be an effective treatment of primary cutaneous B-cell lymphoma [21, 22, 23]. In comparison to intravenous administration, intralesional application of the drug allows the use of lower dosages.


Treatment failures

With rituximab therapy lymphomas can lose CD20 expression and, with that, susceptibility to rituximab. Cutaneous B-cell lymphoma with loss of CD20 immunoreactivity after rituximab therapy has occurred [24, 25]. Relapse of diffuse large B cell lymphoma to CD20-negative multiple cutaneous tumors immediately after anti-CD20 monoclonal antibody (rituximab) therapy has been reported [26].


Treatment of other lymphomas and lymphoma with unique presentations

Some types of lymphoma of the skin can be effectively treated with rituximab. Successful treatment of isolated cutaneous relapse of follicular lymphoma with rituximab has been noted [27]. Cutaneous immunocytoma (which most commonly manifests as extremity based clustered erythematous brown papules) can be treated with rituximab [28]. Intravascular lymphoma commonly presents with skin findings of tender indurated plaques and nodules, but has a rare variant manifesting as telangectatic plaques that can be treated by rituximab [29]. Retreatment with rituximab alone can induce sustained remission in patients with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab [30].

Isolated EBV lymphoproliferative disease in a child with Wiskott-Aldrich syndrome manifesting as cutaneous lymphomatoid granulomatosis responded to treatment with rituximab [31]. EBV-associated cutaneous plasmocytoma in a renal transplant patient has been treated effectively with rituximab [32], [33].


Cryoglobulinemia

Rituximab has been found to be effective therapy of mixed cryoglobulinemia, with decreases in cryoglobulin values and improvement in complement values [34, 35, 36]. In a study of 15 people, Rituximab proved an effective treatment of cryoglobulinemia with skin vasculitis manifestations (ulcers, purpura, and urticaria), subjective symptoms of peripheral neuropathy, low-grade B-cell lymphoma, arthralgias, and fever. Nephritis of recent onset went into remission in one case. Laboratory features, that is, significantly decreased serum rheumatoid factor and cryoglobulins and increased C4, were consistent with the clinical efficacy. Treatment with rituximab is well tolerated, with few infectious complications. Thrombosis of retinal artery or self-limiting panniculitis occurred in one patient each. Rituximab may represent a safe and effective alternative to standard immunosuppression in cryoglobulinemia [37]. Initial increase in the cryoglobulin level after rituximab therapy for type-II cryoglobulinemia secondary to Waldenstrom macroglobulinemia does not indicate failure of response [38].


Collagen Vascular Disease

Rituximab is a promising treatment for systemic lupus erythematosus (SLE) [39, 40]. and dermatomyositis [41]. It can be used for long term therapy of SLE [42] It also might have utility in the treatment of the cutaneous manifestations of lupus [43] This is even true in treatment resistant cases [44, 45]. Treatment complications exist and include extremely high titers of anti-human chimeric antibody following re-treatment with rituximab in a patient with active systemic lupus erythematosus [46]. Rituximab has been used in childhood systemic lupus erythematosus refractory to conventional immunosuppression [47].

Complex cases of SLE have abated with rituximab treatment. Catastrophic systemic lupus erythematosus with Rosai-Dorfman sinus histiocytosis has been treated successfully with rituximab [48]. Saigal reported a case of hypocomplementemic urticarial vasculitis and recurrent angioedema in a patient with systemic lupus erythematosus unresponsive to mycophenolate mofetil, high-dose methylprednisolone, and intravenous immunoglobulin; that patient responded rapidly to rituximab [49]. In summary, systemic autoimmune diseases can respond to rituximab [50].


Hematological diseases

Many hematological diseases are related to pathologic B-cells and the antibodies that they produce. Unsurprisingly, rituximab, which blocks the function of such B-cells, ameliorates a variety of hematologic diseases. Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy has been reported [51]. Rituximab is a useful treatment for adult refractory idiopathic thrombocytopenic purpura [52]. Lian noted a 43-year-old patient who developed factor-V inhibitor 6 months after liver transplantation for primary biliary cirrhosis in association with Sjogren syndrome/systemic lupus erythematosus who suffered from ecchymoses in the lower extremities; rituximab dissipated the factor-V inhibitor after 10 weekly doses of 375-500 mg [53]. B-cell depletion may lead to normalization of anti-platelet, anti-erythrocyte, and antiphospholipid antibodies in systemic lupus erythematosus [54]. Sustained response to rituximab of autoimmune hemolytic anemia associated with antiphospholipid syndrome has been noted [55]. Rituximab was an effective treatment for refractory autoimmune thrombocytopenia in a girl with systemic lupus erythematosus [56].


Waldenstrom's macroglobulinemia

Waldenstrom's macroglobulinemia (WM) is a cancer of mature plasma cells, B lymphocytes, that causes overproduction of monoclonal macroglobulin (IgM antibody). It is sometimes referred to as a lymphoplasmacytic disorder. WM often results in the overproduction of IgM, which causes the blood to become too thick. This hyperviscosity interferes with blood flow through small vessels and leads to many of the symptoms of the disease. Some 35-50 percent of WM patients respond to single rituximab therapy, with limited toxicity [57]. Extended rituximab therapy may lead to more major responses than standard dose rituximab in WM [58].


Pemphigus

Rituximab is a useful treatment for pemphigus vulgaris [59, 60, 61]. This in not surprising because pemphigus is an antibody driven disease and rituximab blocks the function of B-cells and the production of antibodies. Rituximab is even effective treatment for recalcitrant, life-threatening pemphigus vulgaris [62, 63, 64, 65, 66, 67]. This is also true in juvenile pemphigus vulgaris [68]. Treatment-resistant pemphigus foliaceus rapidly responds to rituximab [69].

The use of rituximab can result in the remission of paraneoplastic pemphigus because of its effects on the underlying neoplasm [70, 71, 72, 73]. It is effective treatment for refractory erosive stomatitis secondary to CD20(+) follicular lymphoma-associated paraneoplastic pemphigus [74, 75].


Vasculitis

Autoimmune varieties of vasculitis can be effectively treated with rituximab. Rituximab has been found to be a useful adjunct in the treatment of giant-cell arteritis [76]. Eriksson noted nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab [77]. It has been found to be a useful treatment for refractory Wegener granulomatosis [78], [79, 80, 81]. Keogh noted induction of remission by B-lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis [82]. As vasculitis is a type-III hypersensitivity reaction, which involves antibody immune complex, the decrease of antibody production that rituximab engenders is a useful therapy.


Side Effects


Cutaneous Side effects

The cutaneous side effects of rituximab are frequent but usually not serious. In a study of 356 patients treated in nonrandomized, single-arm studies of rituximab administered as a single agent 44 percent of patient suffered some side effect involving the skin and appendages. Specifically, 15 percent of patients suffered night sweats, 15 percent of patients suffered "skin rash," 14 percent of patients suffered pruritus, and 8 percent suffered urticaria [83]. Observed side-effects in a systemic eight-cycle rituximab therapy in primary cutaneous B-cell lymphomas were two bacterial infections, two patients with shivering during infusion, one patient with sweating for months and one patient with persistent pruritus [84].

In the trial of 356 patients, 2 percent suffered serious cutaneous side effects. The package insert notes a spectrum of serious side effects that include paraneoplastic pemphigus (an uncommon disorder that is a manifestation of the patient's underlying malignancy), Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis [85]. The onset of the reaction in the reported cases has varied from 1 to 13 weeks following rituximab exposure.

Since rituximab's approval, a variety of serious side effects involving the skin have been reported. Several reports note that rituximab can cause serum sickness [86]. Rituximab-induced vasculitis has been reported [87]. Lowndes reported a case of Stevens-Johnson syndrome after treatment with rituximab; it occurred in a 36-year-old man with relapsed follicular lymphoma. The patient developed mucositis and fevers after the first two injections, followed by a florid maculopapular rash with severe orogenital ulceration after the third infusion. Over several weeks his symptoms progressed with severe cutaneous, orogenital and conjunctival ulceration, leading to visual problems and malnutrition. No improvement occurred with steroids and immunosuppressant therapy [88].

Buda-Okreglak described a novel, delayed, proinflammatory syndrome that occurred at or near completion of a 4-week dose-intense course with rituximab in a 58-year-old man with Waldenstrom macroglobulinemia; this syndrome mimicked acute rheumatoid arthritis affecting the hands and the knees [89].

To treat B-cell lymphomas, rituximab (at a dose of 250 mg QW) is sometimes administered with ibritumomab tiuxetan, an immunoconjugate in which the monoclonal antibody ibritumomab is covalently bound to tiuxetan, a high-affinity, linker-chelator for the radioisotopes yttrium-90 (Y-90) or indium-111 (In-111)[90]. The antibody moiety of ibritumomab tiuxetan is ibritumomab, a murine IgG1-κ monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. The tiuxetan chelator provides a stable linkage between the antibody and the radioisotope, permitting radiation to be directed against antigen-positive cells. The β emission from Y-90 induces cell damage by the formation of free radicals in the target and neighboring cells. Severe mucocutaneous reactions, some with fatal outcome, have been reported in association with the ibritumomab tiuxetan therapeutic regimen, which includes rituximab, In-111 ibritumomab tiuxetan, and Y-90.

It is possible that, as an immunosuppressant, rituximab may increase the likelihood for development of cancer. There is one report of Merkel cell carcinoma (MCC) occurring in CLL patients soon after treatment with 2-CdA and/or rituximab, suggesting that this complication rarely observed in CLL patients may have a link with strongly immunosuppressive therapy with 2-CdA and rituximab [91].


Non cutaneous side effects

Although an extensive discussion of noncutaneous side effects in beyond the scope of this paper, a brief survey is useful for physicians contemplating the use of rituximab. Black box warnings include the following [1]:

  • Fatal Infusion Reactions. Deaths within 24 hours of rituximab infusion have been reported. These fatal reactions followed an infusion reaction complex which included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation or cardiogenic shock. Approximately 80 percent of fatal infusion reactions occurred in association with the first infusion.
  • Tumor Lysis Syndrome (TLS). Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of TLS following treatment with rituximab.
  • Severe Mucocutaneous Reactions (discussed above). Severe mucocutaneous reactions, some with fatal outcome, have been reported in association with rituximab treatment.

Other side effects listed in the package insert include the following[1]:

  • Hepatitis B reactivation with related fulminant hepatitis:
  • Hypersensitivity reactions:
  • Serious or life-threatening cardiac arrhythmias (hypotension can occur as well)
  • Severe renal toxicity, including acute renal failure requiring dialysis and, in some cases, a fatal outcome.

Certain precautions should be taken when using rituximab [1]. Because rituximab targets all CD20-positive B lymphocytes, malignant and nonmalignant, complete blood counts (CBC) and platelet counts should be obtained at regular intervals during rituximab therapy and more frequently in patients who develop cytopenias. The duration of cytopenias caused by rituximab can extend well beyond the treatment period. Renal toxicity was seen with this drug in combination with cisplatin in clinical trials. Human antichimeric antibody (HACA) was detected in 4 of 356 patients and 3 had an objective clinical response.

Rituximab can increase the risk of infection [1]. In trials, infectious events occurred in 31 percent of patients: 19 percent of patients had bacterial infections, 10 percent had viral infections, 1 percent had fungal infections, and 6 percent were unknown infections. Serious infectious events including sepsis, occurred in 2 percent of patients. Immune/autoimmune events have been reported, including uveitis, optic neuritis in a patient with systemic vasculitis, pleuritis in a patient with a lupus-like syndrome,

Rixuximab has a variety of hematologic side effects[1]. In clinical trials, series cytopenias were reported in 48 percent of patients treated with rituximab; these include: lymphopenia (40 %), neutropenia (6 %), leukopenia (4 %), anemia (3 percent ), and thrombocytopenia (2 %). The median duration of lymphopenia was 14 days (range 1-588 days) and of neutropenia was 13 days (range, 2 to 116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following rituximab therapy were reported.

The most common respiratory system adverse events experienced were increased cough, rhinitis, bronchospasm, dyspnea, and sinusitis[1]. In both clinical studies and post-marketing surveillance, there have been a limited number of reports of bronchiolitis obliterans presenting up to 6 months post-rituximab infusion and a limited number of reports of pneumonitis (including interstitial pneumonitis) presenting up to 3 months post-rituximab infusion, some of which resulted in fatal outcomes.


Conclusion

Rituximab is a promising agent for the treatment of B-Cell related diseases. It has many side effects, some common and some not common. It has transformed the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, and immune or idiopathic thrombocytopenic purpura. As future research defines the role of the B-cell in disease, the uses of rituximab will likely increase.

References

1. Rituximab Package Insert (Biogen Idec Inc., and Genentech, Inc. 2005) http://www.rituxan.com/rituxan/pi/#alert (accessed August 22, 2005).

2. Goto H, Nishio M, Endo T, Sato N, Koizumi K, Fujimoto K, Sakai T, Kumano K, Obara M, Koike T. Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B-cell lymphoma. Eur J Haematol. 2005;74:526-8.

3. Lacouture ME, Baron JM, Jani AB, Laumann AE, Soltani K. Treatment of radiation-relapsing primary cutaneous B-cell lymphoma with an anti-CD20 monoclonal antibody. Clin Exp Dermatol. 2005;30:46-8.

4. Vedrine L, Fromatin I, Vincent-Salomon A, Decaudin D. Skin lymphomatous lesions treated by rituximab: a necrotic life-threatening evolution. Leuk Lymphoma. 2004;45:1717-8.

5. Prince HM, McCormack C, Ryan G, O'Keefe R, Seymour JF, Baker C. Management of the primary cutaneous lymphomas. Australas J Dermatol. 2003;44:227-40; quiz 241-2.

6. Zinzani PL, Stefoni V, Alinari L, Vianelli N, Baccarani M. Rituximab in heavily pretreated cutaneous B-cell lymphoma.Leuk Lymphoma. 2003;44:1637-8.

7. Viguier M, Bachelez H, Brice P, Rivet J, Dubertret L. Cutaneous B-cell lymphoma treatment with rituximab: two cases Ann Dermatol Venereol. 2002;129(10 Pt 1):1152-5.

8. Dummer R. Immunomodulators in the treatment of cutaneous lymphomas. Expert Opin Biol Ther. 2002;2:279-86.

9. Gellrich S, Muche JM, Pelzer K, Audring H, Sterry W. Anti-CD20 antibodies in primary cutaneous B-cell lymphoma. Initial results in dermatologic patients. Hautarzt. 2001;52:205-10.

10. Heinzerling LM, Urbanek M, Funk JO, Peker S, Bleck O, Neuber K, Burg G, von Den Driesch P, Dummer R. Reduction of tumor burden and stabilization of disease by systemic therapy with anti-CD20 antibody (rituximab) in patients with primary cutaneous B-cell lymphoma. Cancer. 2000;89:1835-44.

11. Heinzerling LM, Urbanek M, Funk JO, Peker S, Bleck O, Neuber K, Burg G, von Den Driesch P, Dummer R. Reduction of tumor burden and stabilization of disease by systemic therapy with anti-CD20 antibody (rituximab) in patients with primary cutaneous B-cell lymphoma. Cancer. 2000;89:1835-44.

12. Sabroe RA, Child FJ, Woolford AJ, Spittle MF, Russell-Jones R. Rituximab in cutaneous B-cell lymphoma: a report of two cases. Br J Dermatol. 2000;143:157-61. 13. 13. Fierro MT, Savoia P, Quaglino P, Novelli M, Barberis M, Bernengo MG. Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. J Am Acad Dermatol. 2003;49:281-7.

14. Lami MC, Vabres P, Dreyfus B, Germain T, Guillet G. Primary cutaneous B-cell lymphoma mimicking pyoderma gangrenosum: first-line treatment with rituximab. Br J Dermatol. 2004;151:250-2.

15. Brogan BL, Zic JA, Kinney MC, Hu JY, Hamilton KS, Greer JP. Large B-cell lymphoma of the leg: clinical and pathologic characteristics in a North American series. J Am Acad Dermatol. 2003;49:223-8.

16. Bonnekoh B, Schulz M, Franke I, Gollnick H. Complete remission of a primary cutaneous B-cell lymphoma of the lower leg by first-line monotherapy with the CD20-antibody rituximab. J Cancer Res Clin Oncol. 2002;128:161-6.

17. Aboulafia DM. Primary cutaneous large B-cell lymphoma of the legs: a distinct clinical pathologic entity treated with CD20 monoclonal antibody (rituximab). Am J Clin Oncol. 2001;24:237-40.

18. Garbea A, Dippel E, Hildenbrand R, Bleyl U, Schadendorf D, Goerdt S. Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer. Br J Dermatol. 2002;146:144-7.

19. Soda R, Costanzo A, Cantonetti M, Orlandi A, Bianchi L, Chimenti S. Systemic therapy of primary cutaneous B-cell lymphoma, marginal zone type, with rituximab, a chimeric anti-CD20 monoclonal antibody. Acta Derm Venereol. 2001;81:207-8.

20. Han K, Haley JC, Carlson K, Pinter-Brown L, Soriano T. Regression of cutaneous intravascular lymphoma with rituximab. Cutis. 2003;72:137-40.

21. Roguedas AM, Watier H, Paintaud G, de Muret A, Vaillant L, Machet L.Intralesional therapy with anti-CD20 monoclonal antibody rituximab: local and systemic efficacy in primary cutaneous B-cell lymphoma. Br J Dermatol. 2005;152:541-4.

22. Paul T, Radny P, Krober SM, Paul A, Blaheta HJ, Garbe C. Intralesional rituximab for cutaneous B-cell lymphoma. Br J Dermatol. 2001;144:1239-43.

23. Heinzerling L, Dummer R, Kempf W, Schmid MH, Burg G. Intralesional therapy with anti-CD20 monoclonal antibody rituximab in primary cutaneous B-cell lymphoma. Arch Dermatol. 2000;136:374-8.

24. Clarke LE, Bayerl MG, Ehmann WC, Helm KF. Cutaneous B-cell lymphoma with loss of CD20 immunoreactivity after rituximab therapy. J Cutan Pathol. 2003;30:459-62.

25. Massengale WT, McBurney E, Gurtler J. CD20-negative relapse of cutaneous B-cell lymphoma after anti-CD20 monoclonal antibody therapy. J Am Acad Dermatol. 2002;46:441-3.

26. Iguchi T, Miyazawa K, Okabe S, Kawakubo K, Shimamoto T, Kuriyama Y, Ito Y, Kimura Y, Ohyashiki K, Serizawa H, Iwaya K, Mukai K. Relapse of diffuse large B cell lymphoma to CD20-negative multiple cutaneous tumors immediately after anti-CD20 monoclonal antibody (rituximab) therapy Rinsho Ketsueki. 2004;45:1129-34.

27. Ferrer A, Lopez-Guillermo A, Montoto S, Estrach T, Colomo L, Montserrat E. Successful treatment of isolated cutaneous relapse of follicular lymphoma with rituximab. Ann Hematol. 2001;80:479-81.

28. Magro CM, Porcu P, Ahmad N, Klinger D, Crowson AN, Nuovo G. Cutaneous immunocytoma: a clinical, histologic, and phenotypic study of 11 cases. Appl Immunohistochem Mol Morphol. 2004;12:216-24.

29. Weichert G, Martinka M, Rivers JK. Intravascular lymphoma presenting as telangectasias: response to rituximab and combination chemotherapy. J Cutan Med Surg. 2003;7:460-3.

30. Cohen Y, Libster D, Da'as N, Amir G, Polliack A. Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab. Hematol J. 2003;4:151-3.

31. Sebire NJ, Haselden S, Malone M, Davies EG, Ramsay AD. Isolated EBV lymphoproliferative disease in a child with Wiskott-Aldrich syndrome manifesting as cutaneous lymphomatoid granulomatosis and responsive to anti-CD20 immunotherapy. J Clin Pathol. 2003;56:555-7.

32. Carbonnelle A, Mahe E, Morelon E, Varet B, Kreis H, Brousse N, Fraitag S. EBV-associated cutaneous plasmocytoma in a renal transplant patient. Ann Dermatol Venereol. 2004;131:1081-4.

33. Donner LR. Epstein-Barr virus-induced transformation of cutaneous plasmacytoma into CD30+ diffuse large B-cell lymphoma. Am J Dermatopathol. 2004;26:63-6.

34. Gertz MA.Cold agglutinin disease and cryoglobulinemia. Clin Lymphoma. 2005;5:290-3.

35. Ghijsels E, Lerut E, Vanrenterghem Y, Kuypers D. Anti-CD20 monoclonal antibody (rituximab) treatment for hepatitis C-negative therapy-resistant essential mixed cryoglobulinemia with renal and cardiac failure. Am J Kidney Dis. 2004;43:e34-8.

36. Uthman I. Pharmacological therapy of vasculitis: an update. Curr Opin Pharmacol. 2004;4:177-82.

37. Zaja F, De Vita S, Mazzaro C, Sacco S, Damiani D, De Marchi G, Michelutti A, Baccarani M, Fanin R, Ferraccioli G. Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood. 2003;101:3827-34.

38. Ghobrial IM, Uslan DZ, Call TG, Witzig TE, Gertz MA. Initial increase in the cryoglobulin level after rituximab therapy for type II cryoglobulinemia secondary to Waldenstrom macroglobulinemia does not indicate failure of response. Am J Hematol. 2004;77:329-30.

39. Sfikakis PP, Boletis JN, Tsokos GC. Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the future. Curr Opin Rheumatol. 2005;17:550-557.

40. Looney RJ. B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis. Rheumatology (Oxford). 2005;44 Suppl 2:ii13-ii17.

41. Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum. 2005;52:601-7.

42. Weide R, Heymanns J, Pandorf A, Koppler H. Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy. Lupus. 2003;12:779-82.

43. Heath M, Raugi GJ. Evidence-based evaluation of immunomodulatory therapy for the cutaneous manifestations of lupus. Adv Dermatol. 2004;20:257-91.

44. Van den Bergh B, Selleslag D, Boelaert JR, Matthys EG, Schurgers M, Vandecasteele S, De Vriese A. Management of therapy-resistant systemic lupus erythematosus with rituximab: report of a case and review of the literature. Acta Clin Belg. 2005;60:102-5.

45. Sabugo S F, Llanos M C, Soto S L, Gutierrez J, Cuchacovich T M. Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: Report of one case. Rev Med Chil. 2005;133:681-4.

46. Saito K, Nawata M, Iwata S, Tokunaga M, Tanaka Y. Extremely high titer of anti-human chimeric antibody following re-treatment with rituximab in a patient with active systemic lupus erythematosus. Rheumatology (Oxford). 2005 Nov;44(11):1462-4.

47. Edelbauer M, Jungraithmayr T, Zimmerhackl LB. Rituximab in childhood systemic lupus erythematosus refractory to conventional immunosuppression: case report. Pediatr Nephrol. 2005;20:811-3.

48. Petschner F, Walker UA, Schmitt-Graff A, Uhl M, Peter HH. "Catastrophic systemic lupus erythematosus" with Rosai-Dorfman sinus histiocytosis. Successful treatment with anti-CD20/rutuximab. Dtsch Med Wochenschr. 2001;126:998-1001.

49. Saigal K, Valencia IC, Cohen J, Kerdel FA. Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of systemic lupus erythematosus: rapid response to rituximab. J Am Acad Dermatol. 2003;49(5 Suppl):S283-5.

50. Gottenberg JE, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A, Larroche C, Soubrier M, Bouillet L, Dougados M, Fain O, Farge D, Kyndt X, Lortholary O, Masson C, Moura B, Remy P, Thomas T, Wendling D, Anaya JM, Sibilia J, Mariette X; Club Rheumatismes et Inflammation (CRI). Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis. 2005;64:913-20.

51. Ahn ER, Lander G, Bidot CJ, Jy W, Ahn YS. Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy. Am J Hematol. 2005;78:127-9.

52. Braendstrup P, Bjerrum OW, Nielsen OJ, Jensen BA, Clausen NT, Hansen PB, Andersen I, Schmidt K, Andersen TM, Peterslund NA, Birgens HS, Plesner T, Pedersen BB, Hasselbalch HC. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. Am J Hematol. 2005;78:275-80.

53. Lian EC, Tzakis AG, Andrews D. Response of factor V inhibitor to rituximab in a patient who received liver transplantation for primary biliary cirrhosis. Am J Hematol. 2004;77:363-5.

54. Tomietto P, Gremese E, Tolusso B, Venturini P, De Vita S, Ferraccioli G. B cell depletion may lead to normalization of anti-platelet, anti-erythrocyte and antiphospholipid antibodies in systemic lupus erythematosus. Thromb Haemost. 2004;92:1150-3.

55. Erdozain JG, Ruiz-Irastorza G, Egurbide MV, Aguirre C. Sustained response to rituximab of autoimmune hemolytic anemia associated with antiphospholipid syndrome. Haematologica. 2004;89:ECR34.

56. ten Cate R, Smiers FJ, Bredius RG, Lankester AC, van Suijlekom-Smit LW, Huizinga TW, Egeler RM. Anti-CD20 monoclonal antibody (rituximab) for refractory autoimmune thrombocytopenia in a girl with systemic lupus erythematosus. Rheumatology (Oxford). 2004;43:244.

57. Bjorkholm M. Treatment options in Waldenstrom's macroglobulinemia. Clin Lymphoma. 2004;5:155-62.

58. Treon SP, Emmanouilides C, Kimby E, Kelliher A, Preffer F, Branagan AR, Anderson KC, Frankel SR; Waldenstrom's Macroglobulinemia Clinical Trials Group. Extended rituximab therapy in Waldenstrom's macroglobulinemia. Ann Oncol. 2005;16:132-8.

59. Herrmann G, Hunzelmann N, Engert A. Treatment of pemphigus vulgaris with anti-CD20 monoclonal antibody (rituximab). Br J Dermatol. 2003;148:602-3.

60. Reynaert S, Black MM. Treating immunobullous diseases: an update. Dermatol Nurs. 2004;16:29-34, 70.

61. Dupuy A, Viguier M, Bedane C, Cordoliani F, Blaise S, Aucouturier F, Bonnetblanc JM, Morel P, Dubertret L, Bachelez H. Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody). Arch Dermatol. 2004;140:91-6.

62. Salopek TG, Logsetty S, Tredget EE. Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, life-threatening pemphigus vulgaris with implications in the pathogenesis of the disorder. J Am Acad Dermatol. 2002;47:785-8.

63. Cooper HL, Healy E, Theaker JM, Friedmann PS. Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (Rituximab). Clin Exp Dermatol. 2003;28:366-8.

64. Virgolini L, Marzocchi V. Anti-CD20 monoclonal antibody (rituximab) in the treatment of autoimmune diseases. Successful result in refractory Pemphigus vulgaris: report of a case. Haematologica. 2003 Jul;88:ELT24.

65. Espana A, Fernandez-Galar M, Lloret P, Sanchez-Ibarrola A, Panizo C. Long-term complete remission of severe pemphigus vulgaris with monoclonal anti-CD20 antibody therapy and immunophenotype correlations. J Am Acad Dermatol. 2004;50:974-6.

66. Morrison LH.Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab). J Am Acad Dermatol. 2004;51:817-9.

67. Wenzel J, Bauer R, Bieber T, Tuting T. Successful rituximab treatment of severe pemphigus vulgaris resistant to multiple immunosuppressants. Acta Derm Venereol. 2005;85:185-6.

68. Schmidt E, Herzog S, Brocker EB, Zillikens D, Goebeler M. Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab. Br J Dermatol. 2005;153:449-51.

69. Goebeler M, Herzog S, Brocker EB, Zillikens D. Rapid response of treatment-resistant pemphigus foliaceus to the anti-CD20 antibody rituximab. Br J Dermatol. 2003;149:899-901.

70. Schadlow MB, Anhalt GJ, Sinha AA. Using rituximab (anti-CD20 antibody) in a patient with paraneoplastic pemphigus. J Drugs Dermatol. 2003;2:564-7.

71. Rossum MM, Verhaegen NT, Jonkman MF, Mackenzie MA, Koster A, Van Der Valk PG, Span LF. Follicular non-Hodgkin's lymphoma with refractory paraneoplastic pemphigus: case report with review of novel treatment modalities. Leuk Lymphoma. 2004;45:2327-32.

72. Jardin F, Levesque H, Tilly H. Auto-immune manifestations in Non-Hodgkin's lymphoma. Rev Med Interne. 2005;26:557-71.

73. Arin MJ, Hunzelmann N. Anti-B- cell-directed immunotherapy (rituximab) in the treatment of refractory pemphigus--an update. Eur J Dermatol. 2005;15:224-30.

74. Borradori L, Lombardi T, Samson J, Girardet C, Saurat JH, Hugli A. Anti-CD20 monoclonal antibody (rituximab) for refractory erosive stomatitis secondary to CD20(+) follicular lymphoma-associated paraneoplastic pemphigus. Arch Dermatol. 2001;137:269-72.

75. Heizmann M, Itin P, Wernli M, Borradori L, Bargetzi MJ. Successful treatment of paraneoplastic pemphigus in follicular NHL with rituximab: report of a case and review of treatment for paraneoplastic pemphigus in NHL and CLL. Am J Hematol. 2001;66:142-4.

76. Bhatia A, Ell PJ, Edwards JC. Anti-CD20 monoclonal antibody (rituximab) as an adjunct in the treatment of giant cell arteritis. Ann Rheum Dis. 2005;64:1099-1100.

77. Eriksson P. Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab. J Intern Med. 2005;257:540-8.

78. Ferraro AJ, Day CJ, Drayson MT, Savage CO. Effective therapeutic use of rituximab in refractory Wegener's granulomatosis. Nephrol Dial Transplant. 2005;20:622-5.

79. Kallenbach M, Duan H, Ring T. Rituximab induced remission in a patient with Wegener's granulomatosis. Nephron Clin Pract. 2005;99:c92-6.

80. Sneller MC. Rituximab and Wegener's granulomatosis: are B cells a target in vasculitis treatment? Arthritis Rheum. 2005;52:1-5.

81. Specks U, Fervenza FC, McDonald TJ, Hogan MC. Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum. 2001;44:2836-40.

82. Keogh KA, Wylam ME, Stone JH, Specks U. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:262-8.

83. Gellrich S, Muche JM, Wilks A, Jasch KC, Voit C, Fischer T, Audring H, Sterry W. Systemic eight-cycle anti-CD20 monoclonal antibody (rituximab) therapy in primary cutaneous B-cell lymphomas--an applicational observation. Br J Dermatol. 2005;153:167-73.

84. Hellerstedt B, Ahmed A. Delayed-type hypersensitivity reaction or serum sickness after rituximab treatment. Ann Oncol. 2003;14:1792.

85. Herishanu Y. Rituximab-induced serum sickness. Am J Hematol. 2002;70:329.

86. Catuogno M, Rezai S, Priori R, Magrini L, Valesini G. Serum sickness associated with rituximab in a patient with hepatitis C virus-related mixed cryoglobulinaemia. Rheumatology (Oxford). 2005;44:406.

87. Dereure O, Navarro R, Rossi JF, Guilhou JJ. Rituximab-induced vasculitis. Dermatology. 2001;203:83-4.

88. Lowndes S, Darby A, Mead G, Lister A. Stevens-Johnson syndrome after treatment with rituximab. Ann Oncol. 2002;13:1948-50.

89. Buda-Okreglak EM, Drabick JJ, Delaney NR. Proinflammatory syndrome mimicking acute rheumatoid arthritis in a patient with Waldenstrom's macroglobulinemia treated with rituximab. Ann Hematol. 2004;83:117-9

90. Zevalin package insert (Biogen Inc. 2005) www.zevalin.com (accessed August 23, 2005)

91. Robak E, Biernat W, Krykowski E, Jeziorski A, Robak T. Merkel cell carcinoma in a patient with B-cell chronic lymphocytic leukemia treated with cladribine and rituximab. Leuk Lymphoma. 2005;46:909-14.

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Title:

A review of rituximab in cutaneous medicine

Journal Issue:

Dermatology Online Journal, 12(1)

Author:

Scheinfeld, Noah

Publication Date:

2006

Publication Info:

Dermatology Online Journal, UC Davis

Permalink:

http://escholarship.org/uc/item/4ns1k655

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