Published papers on the link between CGD carriers and lupus and autoimmunity
Cutaneous and other lupus-like symptoms in carriers of X-linked chronic granulomatous disease: incidence and autoimmune serology.
Cale CM, Morton L, Goldblatt D.
Clin Exp Immunol. 2007 Apr;148(1):79-84.
The objective of this study was to determine the utility of anti-nuclear antibody (ANA) testing in the investigation of cutaneous and other lupus symptoms in female carriers of X-linked chronic granulomatous disease (CGD). We undertook a prospective study of 19 carrier mothers attending our institution, with direct questioning of carriers concerning symptoms and testing for anti-nuclear and anti-phospholipid antibodies. A total of 58% reported significant photosensitive skin rashes, 42% reported mouth ulcers and 37% complained of joint pains that could not be attributed to other known causes. Anti-nuclear antibody (ANA) testing was negative in 73% of all carriers. The five positive ANAs were of low titre (maximum 1 : 320 on Hep 2 cells in two women) and only one weak positive double-stranded DNA antibody and no extractable nuclear antibodies were found. Several of the mothers, despite negative serology, benefited from referral to a specialist, and in some cases to specific treatment. A history of skin rashes, joint pain, fatigue and mouth ulcers should be sought actively in the female relatives of X-CGD patients but negative lupus serology should not preclude referral to appropriate dermatology or rheumatology services, as symptoms may respond well to appropriate treatment.
Abnormal apoptosis in chronic granulomatous disease and autoantibody production characteristic of lupus.
Sanford AN, Suriano AR, Herche D, Dietzmann K, Sullivan KE.
Rheumatology (Oxford). 2006 Feb;45(2):178-81. Epub 2005 Oct 25.
Patients with chronic granulomatous disease and carrier mothers of patients with chronic granulomatous disease are predisposed to developing various forms of lupus. This disorder is a neutrophil defect in intracellular killing. Abnormal apoptosis has been described. We hypothesized that abnormal apoptosis occurring in neutrophils of patients made them more immunogenic. METHODS: Human patients with chronic granulomatous disease were examined for abnormalities of neutrophil apoptosis by flow cytometry. To model the effect of abnormal apoptosis, a murine model was used. Apoptotic cells from either wild type or mice with chronic granulomatous disease were injected into either wild type or chronic granulomatous disease mice and autoantibodies were determined by ELISA. RESULTS: Our studies found that human and murine neutrophils carrying the gp91 form of chronic granulomatous disease had impaired exposure of phosphatidyl serine on the surface. Other markers of apoptosis were largely normal. Injection of apoptotic neutrophils from gp91 knockout mice into gp91 knockout mice led to the development of characteristic autoantibodies of lupus. CONCLUSIONS: Humans with chronic granulomatous disease may be at an increased risk of developing lupus due to abnormal apoptosis and abnormal clearance of apoptotic cells.
Lupus erythematosus tumidus and chronic discoid lupus erythematosus in carriers of X-linked chronic granulomatous disease.
Rupec RA, Petropoulou T, Belohradsky BH, Walchner M, Liese JG, Plewing G, Messer G.
Eur J Dermatol. 2000 Apr-May;10(3):184-9.
Two Caucasian carriers for chronic granulomatous disease (CGD) developed cutaneous lupus erythematosus (LE) with clinically and morphologically characteristic appearance for chronic discoid lupus erythematosus (DLE) and lupus erythematosus tumidus (LET). Direct immunofluorescent examinations and ANA titers were positive in both young women. No systemic involvement due to the ACR criteria was evident. Their sons suffered from X-linked cytochrome-b negative CGD. The diagnosis of CGD was based on measurement of oxidative burst activity by nitroblue tetrazolium (NBT) slide test and by flow cytometry using dihydrorhodamine 123 (DHR). The absence of cytochrome b558 in neutrophilic granulocytes was confirmed photometrically and by flow cytometry using the 7D5 monoclonal antibody against cytochrome b. We report for the first time the association of the photosensitive LE subtype LET and the X-linked CGD carrier state. Tissue damage by UV radiation and a reduced antimicrobial capacity may lead to recurrent immune stimulation and may together with genetic predisposition explain the occurrence of cutaneous LE in female carriers of CGD.
Chronic granulomatous disease: a case study of a symptomatic carrier.
Romera Modamio G, Martín Mateos MA, González Enseñat MA, Pastor Gómez MA.
J Investig Allergol Clin Immunol. 1997 Jan-Feb;7(1):57-61.
An adolescent aged fifteen, with no family history of interest, presented the following cutaneous lesions from the age of two onwards: photosensitive dermatitis in the form of erythematous plaques on the face, purplish erythematous papules on fingers, scaly inflammatory plaques in the nostrils histologically compatible with discoid lupus, and frequent skin infections in the form of folliculitis, furuncles and abscesses (with positive cultures for Staphylococcus aureus) evolving slowly into cold sores in various sites. Slow, partial improvement occurred after treatment with topical corticoids and topical and oral antibiotics. Of the complementary explorations performed, general analysis, immunity and autoimmunity examinations were either negative or normal. The only notable result was the patient's inability to reduce nitroblue tetrazolium (activity 0%). The patient was diagnosed as a carrier of chronic granulomatous disease and treatment based on antibiotic prophylaxis with cotrimoxazole was initiated; skin infections were treated with antiseptic soaps. Subsequent evolution has been favourable, with the gradual resolution and granulation of old lesions and without cutaneous relapses.
Lupus erythematosus-like oral mucosal and skin lesions in a carrier of chronic granulomatous disease. Chronic granulomatous disease carrier genodermatosis.
Lovas JG, Issekutz A, Walsh N, Miller RA.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Jul;80(1):78-82.
We present a case of a young female patient who for 8 years was believed to have discoid lupus erythematosus of the skin and oral mucosae. Only after her infant son had a near-fatal pulmonary infection was the diagnosis of chronic granulomatous disease made and her lupus erythematosus-like mucocutaneous lesions recognized as manifestations of her carrier status for chronic granulomatous disease. The purpose of this report is to raise awareness of and better characterize the mucocutaneous manifestations of carriers of chronic granulomatous disease. Early identification of carriers permits genetic counseling and prenatal diagnosis and forewarns pediatricians so that they can provide better care for affected infants.
Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease.
Sillevis Smitt JH, Weening RS, Krieg SR, Bos JD.
Br J Dermatol. 1990 May;122(5):643-50.
A questionnaire was sent to 16 carriers of the X-linked cytochrome-b558 negative variant of chronic granulomatous disease (CGD). Of the 15 who answered the questionnaire and from data of one additional case, 70% reported recurrent aphthous stomatitis and 63% had recurrent skin eruptions. Five of the carriers (31%) had clinically discoid lupus erythematosus (DLE), although the histopathology was not typical and the immunofluorescence findings were negative. The infiltrate in the lesional skin of three of these patients was analysed using monoclonal antibodies against CD3, CD4, CD8, CDIa, HLA-DR, CDIc, interdigitating cells, B lymphocytes and cells of the monocyte/macrophage lineage. The immunophenotype of the infiltrating cells resembled that found in discoid lupus erythematosus.
Discoid lupus erythematosus-like lesions and stomatitis in female carriers of X-linked chronic granulomatous disease.
Brandrup F, Koch C, Petri M, Schiødt M, Johansen KS.
Br J Dermatol. 1981 May;104(5):495-505.
The skin and oral mucosa were studied in an unselected series of carriers of x-linked chronic granulomatous disease, a hereditary condition in which phagocytic cells display a pronounced functional defect. Three carriers had discoid lupus erythematosus (DLE)-like skin lesions which histopathologically were consistent with DLE of the hypertrophic and profundus type. Four patients had experienced photosensitivity in childhood. Seven patients had recurrent aphthous-like stomatitis which should be distinguished from the recurrent aphthous stomatitis seen in otherwise healthy individuals. The remarkably high incidence of DLE-like symptoms in heterozygous carriers might be related to the presence of mixed populations of defective and normal phagocytes. The variable expression of skin symptoms may be related to uneven distribution of abnormal and normal phagocytes. Female patients with these clinical symptoms, especially the combination of DLE-like skin lesions and aphthous-like stomatitis, should be suspected of being carriers of chronic granulomatous disease and studies of phagocyte function in vitro should be performed, since the diagnosis of the carrier state is of utmost importance for genetic counselling before pregnancy.
Relation of monocyte and neutrophil oxidative metabolism to skin and oral lesions in carriers of chronic granulomatous disease.
Kragballe K, Borregaard N, Brandrup F, Koch C, Staehrjohansen K.
Clin Exp Immunol. 1981 Feb;43(2):390-8.
Out of fifteen carriers of X-linked chronic granulomatous disease five had discoid lupus erythematosus-like skin lesions together with recurrent aphthous-like stomatitis, another five had only recurrent aphthous-like stomatitis, and the remainder were symptom-free. In individual carriers monocytes and neutrophils were equally reduced in their capacity for superoxide production, [1-14C]glucose oxidation and antibody-dependent cytotoxicity; but within he group of carriers a broad spectrum of depression was found. The degree of depression was closely related to the manifestations of clinical disease. It is suggested that the defective oxygen-dependent metabolism might play an aetiological role in the development of inflammatory diseases in carriers of chronic granulomatous disease. Two out of 10 unselected females with discoid lupus erythematosus were shown to be carriers of X-linked chronic granulomatous disease. Screening for this carrier state might therefore be of importance in these patients.
For more on this website about lupus and CGD please see:
CGD and carrier issues
Carrier issues and lupus: 'Q' and 'A' with Dr Cathy Cale
CGD Nurse Study Day: Carrier Issues
Fact sheet No. 8: Lupus
IMPORTANT NOTE :
The information contained on this website is intended only as a guideline, not as a substitute for medical advice. Always consult your doctor if you or your child has any CGD symptoms or concerns.
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