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July 1967, Vol 96, No. 1 >
Article | July 1967

Immunologic Concepts of Light Reactions in Lupus Erythematosus and Polymorphous Light Eruptions: Title and subTitle BreakI. The Mechanism of Action of Hydroxychloroquine

R. S. Lester, MD; T. K. Burnham, MB, BS (London); G. Fine, MD; K. Murray, MD
[+] Author Affiliations

Accepted for publication Jan 20, 1967.

Reprint requests to Department of Dermatology, Henry Ford Hospital, Detroit 48202 (Dr. Burnham).


Detroit

From the departments of dermatology (Drs. Lester, Burnham, and Murray) and pathology (Dr. Fine), Henry Ford Hospital, Detroit.


Arch Dermatol. 1967;96(1):1-10. doi:10.1001/archderm.1967.01610010007001
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References
Comments

Sixty-four patients were light tested to determine the relationships between systemic and discoid lupus erythematosus (SLE, DLE) and polymorphous light eruption (PMLE) in immunopathologic responses to light and the mechanism of action of antimalarial drugs. The effects of intradermal hydroxychloroquine sulfate (Plaquenil), methylprednisolone sodium succinate (Solu-Medrol), methotrexate, and saline, and topical applications of hydroxychloroquine and saline on cutaneous responses to ultraviolet light were studied in a smaller group. There was significant diminution of delayed erythema and blocking of the reproduced eruptions almost only at the intradermal hydroxychloroquine site in five (SLE, 1; DLE, 2; and PMLE, 2) out of seven positive lighttest reactors. The incidence of positive light tests was higher in the antinuclear factor (ANF) tests (11.1%) suggesting a more active disease state in the ANF positive PMLE patients. Antimalarial drugs may conceivably act by interfering with complement activity at the local tissue level in SLE, DLE, and PMLE or by deoxyribonucleic acid binding.

REFERENCES

1 +
Burnham, T.K.; Fine, G.; and Neblett, T.R.:  The Immunofluorescent Tumor Imprint Technique: II. The Frequency of Antinuclear Factors in Connective Tissue Disease and Dermatoses , Ann Intern Med 65:9-19, 1966;.
2 +
Mellors, R.C.; Ortega, L.C.; and Holman, H.R.:  Role of γ in the Pathogenesis of Renal Lesions in Systemic Lupus Erythematosus and Chronic Membranous Glomerulonephritis, With an Observation on the Lupus Erythematosus Cell Reaction , J Exp Med 106:191-201, 1957;.
3 +
Burnham, T.K.; Neblett, T.R.; and Fine, G.:  The Application of the Fluorescent Antibody Technique to the Investigation of Lupus Erythematosus and Various Dermatoses , J Invest Derm 41:451-456, 1963;.
4 +
Cormane, R.H.: " Bound" Globulin in the Skin of Patients With Chronic Discoid Lupus Erythematosus and Systemic Lupus Erythematosus , Lancet 1:534-535, 1964;.
5 +
Tan, E.M., and Kunkel, H.G.:  An Immunofluorescent Study of the Skin Lesions in Systemic Lupus Erythematosus , Arthritis Rheum 9:37-46, 1966;.
6 +
Ten Have-Opbroek, A.A.W.:  Demonstration of Immunoglobulins and Complement in the Skin of Patients With Lupus Erythematosus , Acta Dermatovener 46:68-71, 1966;.
7 +
Kalsbeek, G.L., and Cormane, R.H.: " Bound" Complement in the Skin of Patients With Chronic Discoid Lupus Erythematosus and Systemic Lupus Erythematosus , Lancet 2:178-180, 1964;.
8 +
Elliott, J.A., Jr., and Mathieson, D.R.:  Complement in Disseminated (Systemic) Lupus Erythematosus , Arch Derm 68:119-128, 1953;.
9 +
Cahn, M.M.; Levy, E.J.; and Shaffer, B.:  Polymorphous Light Eruption: A Ten-Year Follow-up and Evaluation , Arch Derm 88:756-758, 1963;.
10 +
Epstein, J.H.:  Polymorphous Light Eruptions: Phototest Technique Studies , Arch Derm 85:502-504, 1962;.
11 +
Burnham, T.K.; Fine, G.; and Neblett, T.R.:  Tumor Imprints as a Source of Nuclear Substrate for the Detection of Antinuclear Factors , J Invest Derm 43:7-9, 1964;.
12 +
Burnham, T.K.; Neblett, T.R.; and Fine, G.:  The Immunofluorescent Tumor Imprint Technique: I. Description and Evaluation , Amer J Clin Path 45:714-721, 1966;.
13 +
Epstein, J.H.; Tuffanelli, D.L.; and Dubois, E.L.:  Light Sensitivity and Lupus Erythematosus , Arch Derm 91:483-485, 1965;.
14 +
Peterson, W.C., Jr., and Fusaro, R.M.:  Antinuclear Factor in Light Sensitivity and Lupus Erythematosus , Arch Derm 87:563-565, 1963;.
15 +
Laurell, A.B., et al:  Complement Components in Three Pathological Sera: Relation to Clinical States , Clin Exp Immun 1:13-23, 1966;.
16 +
Cahn, M.M.; Levy, E.J.; and Shaffer, B.:  Polymorphous Light Eruption: The Effect of Chloroquine Phosphate in Modifying Reactions to Ultra-Violet Light , J Invest Derm 26:201-207, 1956;.
17 +
Sams, W.M., Jr., and Carroll, N.V.:  The "Spectral Shift" Phenomenon of Chloroquine , Arch Derm 93:123-128, 1966;.
18 +
Thomas, E.D., et al:  The Effect of Methotrexate on Antibody Production in the Dog , Blood 20:112, 1962;.
19 +
Sams, W.M., Jr., and Epstein, J.H.:  The Affinity of Melanin for Chloroquine , J Invest Derm 45:482-487, 1965;.
20 +
Baer, R.L., and Harber, L.C.:  Photobiology of Lupus Erythematosus , Arch Derm 92:124-128, 1965;.
21 +
Zvaifler, N.J.:  The Subcellular Localization of Chloroquine and Its Effect on Lysosomal Disruption , abstracted, Arthritis Rheum 7:760-761, 1964;.
22 +
Weissmann, G.:  Lysosomes , New Eng J Med 273:1143-1149, 1965;.
23 +
Weissmann, G., and Dingle, J.:  Release of Lysosomal Protease by Ultra-Violet Irradiation and Inhibition by Hydrocortisone , Exp Cell Res 25:207-210, 1961;.
24 +
Stollar, D., and Levine, L.:  Antibodies to Denatured Deoxyribonucleic Acid in Lupus Erythematosus Serum: V. Mechanism of DNA-Anti-DNA Inhibition by Chloroquine , Arch Biochem 101:335-341, 1963;.
25 +
Kurnick, N.B., and Radcliffe, I.E.:  Reaction Between DNA and Quinacrine and Other Antimalarials , J Lab Clin Med 60:669-688, 1962;.
26 +
Neblett, T.R.; Burnham, T.K.; and Kay, N.:  Chloroquine: Its Mechanism of Action Upon Immune Phenomena , Arch Derm 92:720-725, 1965;.

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1 +
Burnham, T.K.; Fine, G.; and Neblett, T.R.:  The Immunofluorescent Tumor Imprint Technique: II. The Frequency of Antinuclear Factors in Connective Tissue Disease and Dermatoses , Ann Intern Med 65:9-19, 1966;.
2 +
Mellors, R.C.; Ortega, L.C.; and Holman, H.R.:  Role of γ in the Pathogenesis of Renal Lesions in Systemic Lupus Erythematosus and Chronic Membranous Glomerulonephritis, With an Observation on the Lupus Erythematosus Cell Reaction , J Exp Med 106:191-201, 1957;.
3 +
Burnham, T.K.; Neblett, T.R.; and Fine, G.:  The Application of the Fluorescent Antibody Technique to the Investigation of Lupus Erythematosus and Various Dermatoses , J Invest Derm 41:451-456, 1963;.
4 +
Cormane, R.H.: " Bound" Globulin in the Skin of Patients With Chronic Discoid Lupus Erythematosus and Systemic Lupus Erythematosus , Lancet 1:534-535, 1964;.
5 +
Tan, E.M., and Kunkel, H.G.:  An Immunofluorescent Study of the Skin Lesions in Systemic Lupus Erythematosus , Arthritis Rheum 9:37-46, 1966;.
6 +
Ten Have-Opbroek, A.A.W.:  Demonstration of Immunoglobulins and Complement in the Skin of Patients With Lupus Erythematosus , Acta Dermatovener 46:68-71, 1966;.
7 +
Kalsbeek, G.L., and Cormane, R.H.: " Bound" Complement in the Skin of Patients With Chronic Discoid Lupus Erythematosus and Systemic Lupus Erythematosus , Lancet 2:178-180, 1964;.
8 +
Elliott, J.A., Jr., and Mathieson, D.R.:  Complement in Disseminated (Systemic) Lupus Erythematosus , Arch Derm 68:119-128, 1953;.
9 +
Cahn, M.M.; Levy, E.J.; and Shaffer, B.:  Polymorphous Light Eruption: A Ten-Year Follow-up and Evaluation , Arch Derm 88:756-758, 1963;.
10 +
Epstein, J.H.:  Polymorphous Light Eruptions: Phototest Technique Studies , Arch Derm 85:502-504, 1962;.
11 +
Burnham, T.K.; Fine, G.; and Neblett, T.R.:  Tumor Imprints as a Source of Nuclear Substrate for the Detection of Antinuclear Factors , J Invest Derm 43:7-9, 1964;.
12 +
Burnham, T.K.; Neblett, T.R.; and Fine, G.:  The Immunofluorescent Tumor Imprint Technique: I. Description and Evaluation , Amer J Clin Path 45:714-721, 1966;.
13 +
Epstein, J.H.; Tuffanelli, D.L.; and Dubois, E.L.:  Light Sensitivity and Lupus Erythematosus , Arch Derm 91:483-485, 1965;.
14 +
Peterson, W.C., Jr., and Fusaro, R.M.:  Antinuclear Factor in Light Sensitivity and Lupus Erythematosus , Arch Derm 87:563-565, 1963;.
15 +
Laurell, A.B., et al:  Complement Components in Three Pathological Sera: Relation to Clinical States , Clin Exp Immun 1:13-23, 1966;.
16 +
Cahn, M.M.; Levy, E.J.; and Shaffer, B.:  Polymorphous Light Eruption: The Effect of Chloroquine Phosphate in Modifying Reactions to Ultra-Violet Light , J Invest Derm 26:201-207, 1956;.
17 +
Sams, W.M., Jr., and Carroll, N.V.:  The "Spectral Shift" Phenomenon of Chloroquine , Arch Derm 93:123-128, 1966;.
18 +
Thomas, E.D., et al:  The Effect of Methotrexate on Antibody Production in the Dog , Blood 20:112, 1962;.
19 +
Sams, W.M., Jr., and Epstein, J.H.:  The Affinity of Melanin for Chloroquine , J Invest Derm 45:482-487, 1965;.
20 +
Baer, R.L., and Harber, L.C.:  Photobiology of Lupus Erythematosus , Arch Derm 92:124-128, 1965;.
21 +
Zvaifler, N.J.:  The Subcellular Localization of Chloroquine and Its Effect on Lysosomal Disruption , abstracted, Arthritis Rheum 7:760-761, 1964;.
22 +
Weissmann, G.:  Lysosomes , New Eng J Med 273:1143-1149, 1965;.
23 +
Weissmann, G., and Dingle, J.:  Release of Lysosomal Protease by Ultra-Violet Irradiation and Inhibition by Hydrocortisone , Exp Cell Res 25:207-210, 1961;.
24 +
Stollar, D., and Levine, L.:  Antibodies to Denatured Deoxyribonucleic Acid in Lupus Erythematosus Serum: V. Mechanism of DNA-Anti-DNA Inhibition by Chloroquine , Arch Biochem 101:335-341, 1963;.
25 +
Kurnick, N.B., and Radcliffe, I.E.:  Reaction Between DNA and Quinacrine and Other Antimalarials , J Lab Clin Med 60:669-688, 1962;.
26 +
Neblett, T.R.; Burnham, T.K.; and Kay, N.:  Chloroquine: Its Mechanism of Action Upon Immune Phenomena , Arch Derm 92:720-725, 1965;.

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