Two cases of atopic dermatitis associated with autoimmune abnormalities

I. Sekigawa, T. Yoshiike1, N. Iida, H. Hashimoto2 and H. Ogawa3

Department of Medicine and
1 Department of Dermatology, Juntendo University Izu-Nagaoka Hospital, Shizuoka and
2 Department of Internal Medicine and Rheumatology and
3 Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan

SIR, The relationship between allergic disorders [such as atopic dermatitis (AD), asthma, allergic rhinitis and conjunctivitis] and systemic lupus erythematosus (SLE) and/or mixed connective tissue disease (MCTD) is still unclear and controversial [14]. Certain reports have indicated a high incidence of these allergic diseases in SLE patients, but other reports have denied this [13]. The prevalence of AD in the children of mothers with SLE is known to be higher than in normal controls [4]. There has been no clear evidence of a higher serum concentration of immunoglobulin (Ig) E in SLE/MCTD patients when compared with normal controls, although IgE levels are reported to change according to disease activity [1, 2]. Our recently encountered patients with AD and autoimmune abnormalities seem to be interesting with respect to this issue.

The first patient was a 20-yr-old woman who was admitted to our hospital complaining of spiking fever and myalgia. She had suffered from severe AD for 10 yr. On admission, blood tests showed a white blood cell (WBC) count of 8.4x103/mm3, a red blood cell (RBC) count of 381x104/mm3, a haemoglobin (Hb) concentration of 10.9 g/dl and a platelet count of 23.3x104/mm3. The levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were 120 IU/l (normal range 10–40 IU/l), 83 IU/l (normal range 5–40 IU/l) and 1189 IU/l (normal range 200–450 IU/l) respectively, while creatine kinase and aldolase were 2395 IU/l (normal range 40–200 IU/l) and 13.4 IU/l (normal range 1.7–5.7 IU/l) respectively. The erythrocyte sedimentation rate (ESR) was 59 mm/h and C-reactive protein (CRP) was 3.3 mg/dl (normally<0.3 mg/dl). Proteinuria and renal dysfunction were not detected. Her immunological findings are summarized in Table 1Go. On the basis of clinical and laboratory findings, she was diagnosed as having myositis associated with MCTD-like immune abnormalities and was given prednisolone therapy (40 mg/day). The treatment was effective in controlling her symptoms. One year later, she was readmitted to our hospital with hypersensitivity pneumonitis with an unknown cause. After hospitalization, her symptoms and the abnormalities on the chest X-ray film showed spontaneous improvement. She is now being treated with low-dose steroid therapy (5 mg/day) and no exacerbation of myositis has occurred, although her AD has not completely resolved.


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TABLE 1. Immunological findings in the two patients

 
The second patient was a 21-yr-old man who had suffered from severe AD since childhood [5]. He was admitted to our hospital complaining of spiking fever and chest pain, with herpes zoster infection on the chest wall. Laboratory tests gave the following results: WBC, 3.3x103/mm3; RBC, 400x104/mm3; Hb, 11.9 g/dl; platelets, 5.8x104/mm3; GOT, 445 IU/l; GPT, 424 IU/l; LDH, 2411 IU/l; ESR, 17 mm/h; CRP, 3.3 mg/dl; and ferritin, 1218 ng/ml (normal range 27–320 ng/ml). The main immunological findings are shown in Table 1Go. The serum levels of several cytokines, such as interleukin (IL)-6 and IL-10, were also elevated. Clinical and laboratory data allowed us to exclude malignancy, as well as viral infections other than herpes zoster. The bone marrow showed characteristic features of haemophagocytosis. After admission, cytopenia (mainly lymphocytes and platelets) rapidly became worse and shock was caused by the viral infection. Plasma exchange therapy was performed in addition to the administration of acyclovir and prednisolone, and these treatments were effective. He was thought to have virus-associated haemophagocytic syndrome (VAHS) with MCTD-like immune abnormalities. The steroid dose was gradually tapered without exacerbation of VAHS, his MCTD-like manifestations and his AD.

Neither patient has developed any other allergic disease, such as asthma, rhinitis or conjunctivitis.

These two patients had AD with manifestations similar to those of MCTD (such as Raynaud's phenomenon and a high titre of anti-RNP antibodies). However, they did not strictly fulfil the criteria for a diagnosis of MCTD [6], because the first patient did not show SLE- and progressive systemic sclerosis (PSS)-like findings and the second patient did not have polymyositis- and PSS-like findings, as indicated in the criteria. Both patients showed hyper-responsiveness to exogenous antigens (such as hypersensitivity pneumonitis or VAHS). A decrease in the CD4+ to CD8+ T-cell ratio (CD4/CD8 ratio) and an increase in activated CD8+ T cells [implied by the expression of human leucocyte antigen (HLA) DR] are generally observed in patients with SLE/MCTD [7, 8]. These phenotypic characteristics of peripheral lymphocytes were not found in either patient (Table 1Go), although we cannot exclude the influence of myositis and VAHS on phenotypic expression in these patients. In general, exogenous and endogenous antigens are recognized by CD4+ and CD8+ T cells respectively [8]. A decrease in the CD4/CD8 ratio in SLE occurs because CD8+ T cells activated by endogenous antigens, such as endogenous retroviruses and/or cell-derived cytokines such as IL-16 (which uses CD4 molecules as its receptor), stimulate CD4+ T cells and cause the number of these cells to decrease (probably due to apoptosis). In fact, the CD4/CD8 ratio in SLE/MCTD is inversely correlated with the increased HLA-DR expression by CD8+ T cells [8]. In contrast, the CD4/CD8 ratio is increased in AD due to enrichment with CD4+ T cells [9]. The ratio seems to reflect the process of recognizing endogenous antigens in SLE/MCTD and exogenous antigens in AD, on the basis of the hyper-responsiveness to antigens that is common to the two diseases [10]. It seems that the coexistence of two diseases with different trends in CD4/CD8 ratio is rare, and that one such disease should normally occur without the other. Our recent analysis (matched for race, age, sex, and region) revealed that the frequency of allergic diseases, including AD, is not increased in SLE patients compared with normal controls {the frequency of AD in SLE patients and controls (n=52 for both groups) was 6 vs 15%; [15]}. Although there have been no reports suggesting a high incidence of the coexistence of MCTD with allergic diseases, including AD, our two patients suggest that further investigations are needed to clarify the relationship between SLE/MCTD and allergic disorders.

Notes

Correspondence to: I. Sekigawa, Department of Medicine, Juntendo University Izu-Nagaoka Hospital, 1129 Nagaoka, Izu-Nagaoka-cho, Tagata-gun, Shizuoka 410-2295, Japan. E-mail: sekigawa{at}mtd.biglobe.ne.jp Back

References

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Accepted 21 May 2002





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