Cameo Oxford, UK International IJD Blackwell 0011-9059 45 Publishing Journal Ltd, Ltd. of Dermatology 2003
Lupus erythematosus-like lesions in a carrier of X-linked chronic granulomatous disease: A case report and personal considerations Lupus-like Foti CAMEO et al. lesions and chronic granulomatous disease
Caterina Foti, MD, Nicoletta Cassano, MD, Baldassarre Martire, MD, Raffaele Filotico, MD, Valentina Mastrandrea, MD, and Gino A. Vena, MD
From the Unit of Dermatology, Department of Internal Medicine, Immunology and Infectious Diseases, the Department of Pediatrics (Biomedicina dell’Età Evolutiva), University of Bari, and the Istituto Dermopatico dell’Immacolata, I.D.I., I.R.C.C.S., Rome, Italy Correspondence Prof C. Foti, MD Unit of Dermatology Department of Internal Medicine Immunology and Infectious Diseases University of Bari Policlinico, Piazza Giulio Cesare, 11 I-70124 Bari Italy E-mail:
[email protected]
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A 46-year-old woman presented with erythematous plaques over the left aspect of the neck (Fig. 1), the décolleté and the midback of 1 month’s duration. The lesions had been gradually enlarging peripherally and were asymptomatic; they were not scaling and did not appear to be induced or worsened by sun-exposure. The patient reported to suffer from dysthyroidism and polyposis of the colon and uterus and to have a son affected with chronic granulomatous disease (CGD). She had been taking no concomitant medications. Physical examination revealed infiltrated, erythematous, figurate plaques, 2 to 5 cm in diameter, with intensely erythematosus borders. There was left laterocervical lymphoadenopathy. Laboratory investigations showed hypergammaglobulinemia with increased serum levels of IgG and IgA isotypes. Circulating immune complexes, serum complement, rheumatoid factor, antinuclear antibodies, LE cell, and antidsDNA, anti-Ro / SS-A and anti-La / SS-b were absent. At the capillaroscopic examination of the nail folds, there were scanty asphyxial loops without signs of evident microangiopathy. Chest X-ray, ultrasound of the abdomen, standardized phototesting and photoprovocation testings were without relevant findings. Delayed hypersensitivity skin tests were negative, and lymphocyte immunophenotype was strictly International Journal of Dermatology 2004, 43, 840 –842
Figure 1 Erythematous plaques over the left aspect of the neck in
a carrier of X-linked chronic granulomatous disease
normal. Histopathology showed flattening of the epidermis with focal signs of modest hyperkeratosis and focal liquefaction degeneration of the basal layer of the appendages. An inflammatory infiltrate, predominantly lymphocytic, was found around the appendages and the blood vessels. The basement membrane was thickened and strongly stained with © 2004 The International Society of Dermatology
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Figure 2 Photomicrograph showing flattening of the epidermis
with focal signs of modest hyperkeratosis, focal liquefaction degeneration of the basal layer of the appendages and thickening of the basement membrane stained with periodic acid-Shiff; presence of inflammatory infiltrate, mainly lymphocytic, around the appendages and the blood vessels (PAS ×10)
periodic acid-Schiff (Fig. 2). Deposits of IgG, IgA, IgM and C3 were not present. Flow cytometric analysis of granulocyte respiratory burst by dihydrorhodamine 123 in neutrophils stimulated with phorbol 12-myristate 13-acetate1 displayed two distinct subsets of neutrophils: with normal (30% of cells) and defective oxidative burst activity, respectively, indicating the carrier state for CGD. Skin lesions cleared after treatment with topical corticosteroids. At 18-months’ follow up, the rash tended to relapse, even if with lesions less diffuse and severe than previously, which were well-controlled by intermittent application of corticosteroid preparations. Cutaneous scarring and laboratory abnormalities did not occur. Discussion Chronic granulomatous disease is a rare inherited disorder of phagocytes in which defective production of reactive oxygen intermediates impairs the intracellular killing of microrganisms and predisposes patients to recurrent severe bacterial and fungal infections. The X-linked form of CGD, accounting for approximately 70% of cases overall, results from the absence of cytochrome b558 beta-chain (gp91phox) of the phagocyte oxidase complex (NADPH-oxidase). Female carriers of CGD exhibit a variable reduction in the oxidative burst activity, which is usually sufficient to induce an effective killing of infectious agents. A great variety of pathological conditions have been frequently reported in female carriers of CGD, including discoid lupus erythematosus (DLE), DLElike lesions, Jessner benign lymphocytic infiltration of the © 2004 The International Society of Dermatology
Lupus-like lesions and chronic granulomatous disease Cameo
skin, apthous stomatitis, photosensitivity, and Raynaud’s phenomenon.2–10 Our patient presented with lesions similar to those regarded previously by other authors as DLE-like. Clinical discriminating features of DLE absent in this “DLE-like” rash are follicular plugging, adherent scaling, and atrophic scarring. The patient did not present photosensitivity, systemic symptoms, serologic or immunofluorescence anomalies. Our data indicate that the rash observed in carriers of CGD could be a unique dermatosis, distinct from lupus erythematosus, as previously suggested.9 It has been speculated that a similar pathogenic mechanism can underlie these two disorders.3 In particular, the diminished activity of a phagocyte oxidative burst in carriers of CGD may result in delayed clearance of microbial or cell-derived antigens. In turn, the persistence of molecules with immunogenic potential can stimulate the normal population of phagocytes to release proteolytic enzymes with subsequent tissue damage. Anyway, the observation of similar lesions in women should lead one to suspect defective respiratory burst activity and to monitor for the development of signs of lupus erythematosus. In the absence of an unanimous and definitive nosologic assignment, there are also ambiguous data concerning the therapeutic management of this “lupuslike” rash. Probably, treatment has to be tailored to clinical and laboratory findings, with antimalarials reserved in case of photosensitivity or other associated symptoms. In our patient skin lesions were controlled by topical corticosteroids, applied intermittently as needed. References 1 Vowells SJ, Sekhsaria S, Malech HL, et al. Flow cytometric analysis of the granulocyte respiratory burst: a comparison study of fluorescent probes. J Immunol Meth 1995; 178: 89 – 97. 2 Nelson CE, Dahl MV, Goltz RW. Arcuate dermal erythema in a carrier of chronic granulomatous disease. Arch Dermatol 1977; 113: 798 – 800. 3 Brandrup F, Koch C, Petri M, et al. Discoid lupus erythematosus-like lesions and stomatitis in female carriers of X-linked chronic granulomatous disease. Br J Dermatol 1981; 104: 495 – 504. 4 Barton LL, Johnson CR. Discoid lupus erythematosus and X-linked chronic granulomatous disease. Pediatr Dermatol 1986; 3: 376 – 379. 5 Garioch JJ, Sampson JR, Seyright M, et al. Dermatoses in five related female carriers of X-linked chronic granulomatous disease. Br J Dermatol 1989; 121: 391 – 396. 6 Sillevis Smitt JH, Weening RS, Krieg SR, et al. Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. Br J Dermatol 1990; 122: 643 – 650. 7 Hafner J, Enderlin A, Seger RA, et al. Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. Br J Dermatol 1992; 127: 446 – 447. International Journal of Dermatology 2004, 43, 840 –842
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8 Rupec RA, Petropoulou T, Belohradsky BH, et al. Lupus erythematosus tumidus and chronic discoid lupus erythematosus in carriers of X-linked chronic granulomatous disease. Eur J Dermatol 2000; 10: 184 – 189. 9 Chowdhury MM, Anstey A, Matthews CN. The dermatosis
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of chronic granulomatous disease. Clin Exp Dermatol 2000; 25: 190 – 194. 10 Córdoba-Guijarro S, Feal C, Daudén E, et al. Lupus erythematosus-like lesions in a carrier of X-linked chronic granulomatous disease. J Eur Acad Dermatol Venereol 2000; 14: 409 – 411.
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Chronic telogen effluvium or early androgenetic alopecia? Chronic telogen effluvium or early androgenetic alopecia?
Rodney Sinclair, MBBS, FACD
From the Department of Dermatology, University of Melbourne, Department of Medicine, Monash University, and Skin and Cancer Foundation of Victoria, Melbourne, Vic., Australia Correspondence Rodney Sinclair, MBBS, FACD Department of Dermatology University of Melbourne St Vincent’s Hospital 41 Victoria Parade Fitzroy, 3065 Australia E-mail:
[email protected]
A 16-year-old girl presented with a 12-month history of generalized hair shedding from the scalp. The onset of shedding coincided with the development of Hashimoto’s thyroiditis and iron deficiency. At the time of initial presentation, the Hashimoto’s thyroiditis had been treated with Neo-Mercazole and she was euthyroid. Her iron stores were low, with a ferritin level of 13 µg/ L. As she was vegetarian, oral iron replacement therapy was commenced without further investigation. On follow-up 6 months later, her iron stores were normal (ferritin, 36 µg / L), but the hair shedding had continued. On examination, there was a positive hair pull test from both the vertex of the scalp and the occipital scalp. There was mild bitemporal recession, but no widening of the central part, and she appeared to have a full, thick head of hair (Fig. 1). Additional investigations at that time revealed normal thyroid function and negative antinuclear antibody (ANA) and syphilis serology. She was on no medication other than Neo-Mercazole. Serum testosterone, dihydroepiandosterone sulphate (DHEAS) and sex hormone binding globulin (SHBG) were normal. Two 4-mm punch biopsies were taken from the vertex of the scalp; one was sectioned horizontally and the other vertically. The vertical section was unremarkable. On the horizontal section, there were 32 hair follicles in total, 30 of which were terminal hairs and two of which were vellus hairs. One hair was in telogen. The ratio of terminal to vellus hairs was 15 : 1. A diagnosis of chronic telogen effluvium was made. The condition was explained to the patient and she was reassured that chronic telogen effluvium is not a progressive condition and does not lead to baldness. No treatment was recommended. At follow-up 12 months later, the hair loss had obviously progressed and the patient was assessed as having Ludwig Stage 1 androgenetic alopecia with widening of the central part (Fig. 2). Repeat blood tests showed normal iron studies, thyroid function, and hormone parameters. Three 4-mm punch biopsies were taken from the vertex of the scalp and all were sectioned horizontally. The terminal to vellus hair ratios were 1 : 1, 2.6 : 1, and 1.9 : 1. A diagnosis of androgenetic alopecia was made and she was commenced on oral spironolactone, 200 mg / day.
Discussion Chronic telogen effluvium (CTE) was described as a primary idiopathic disease entity in 1996.1 In CTE, women present with generalized shedding of telogen hairs from the scalp in association with bitemporal recession. Importantly, there is no widening of the central part and the women present with International Journal of Dermatology 2004, 43, 842 840 –843 –842
a full, thick head of hair. Other important causes of hair loss, such as androgenetic alopecia (AA), thyroid disease, druginduced hair loss, systemic lupus erythematosus, and nutritional deficiency, require exclusion.2 CTE can be differentiated from early AA histologically. For diagnosis, two 4-mm punch biopsies should be taken from the vertex scalp, with one sectioned vertically and the other © 2004 The International Society of Dermatology
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Figure 1 Initial presentation
horizontally. On horizontal sectioning, the ratio of terminal to vellus hairs is used to indicate follicle miniaturization, the hallmark of AA. A ratio of less than 4 : 1 is considered to be pathognomonic of AA, whereas a ratio of greater than 8 : 1 indicates CTE.3 The prognosis for women with CTE is uncertain. It has been reported that hair shedding follows a fluctuating course, that women with this condition do not go bald, and that the condition usually resolves after a number of years.1 The initial misdiagnosis in this case highlights that a single horizontally sectioned 4-mm punch biopsy may not be large enough to exclude a diagnosis of female AA. Although it is possible that this patient initially had CTE and then went on to develop advanced AA in the space of 12 months, it is more likely that the initial assessment failed to diagnose AA due to a sampling error.
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Chronic telogen effluvium or early androgenetic alopecia? Cameo
Figure 2 Presentation after 12 months
This case also highlights that women with AA may present with a diffuse reduction in hair density on the crown, chronic increased telogen hair shedding, or both. Ipso facto, women who present with increased telogen hair shedding of more than 6 months’ duration, without any discernible reduction in hair density over the crown, may have either chronic diffuse telogen hair loss or AA, and we advocate further investigation to differentiate between these two conditions. References 1 Whiting DA. Chronic telogen effluvium: increased scalp hair shedding in middle-aged women. J Am Acad Dermatol 1996; 35: 899 – 906. 2 Sinclair RD. Diffuse hair loss. Int J Dermatol 1999; 38: 8 –18. 3 Whiting DA. Scalp biopsy as a diagnostic and prognostic tool in androgenetic alopecia. Dermatol Ther 1998; 8: 24 – 33.
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