Misako Tanaka

Prurigo nodularis Consists of Two Distinct Forms: Early-Onset Atopic and Late-Onset Non-Atopic

BACKGROUND Prurigo nodularis (PN) is a characteristic chronic dermatosis of unknown etiology showing severely pruritic nodules mainly on the extremities. Atopic diathesis has been implicated as a contributing factor. OBJECTIVE Our purpose was to analyze the role of environmental allergens from living organisms in the pathogenesis of PN, to report hypersensitivity against various environmental allergens and to relate this to atopic history in 31 PN patients. METHODS Positive and negative controls were studied including 52 patients with atopic dermatitis (AD) and 22 healthy controls. RAST, prick tests and scarification patch tests were performed on the patients and specimens from lesions of 8 patients were stained with anti-eosinophil cationic protein (ECP) antibody. RESULTS The 31 PN patients were divided into two groups, those with a past or present history of AD (PN + AD patients) and those without (PN-only patients). Twenty patients (65%) had PN + AD (median age at onset 19 years) and 11 (35%) had PN only (median age at onset 48 years). Analyses of serum IgE levels. RAST scores, prick test and scarification patch test results revealed that the PN + AD patients showed hypersensitive reactions to the environmental allergens in a pattern almost identical to that noted in AD without PN. In contrast, most of those with PN only did not show any hypersensitivity reactions to the environmental allergens. Histologically, many activated eosinophils, identified by monoclonal antibody to ECP, were observed only in the dermis of the PN+AD patients, in contrast to few eosinophils in the lesion of PN-only patients. CONCLUSIONS These results indicate that there are two forms of PN: an atopic and a non-atopic one. The PN+AD group is closely associated with AD, being accompanied by cutaneous hypersensitivity to various environmental allergens (a pattern similar to that displayed by AD patients) and has a younger age of onset, whereas the PN-only group, which showed a much older age of onset, does not show any such hypersensitive reactions against these allergens.

Normal recovery of the stratum corneum barrier function following damage induced by tape stripping in patients with atopic dermatitis

Patients with atopic dermatitis (AD) constantly inflict mechanical damage to their skin by scratching induced by pruritus. On excoriated lesions of the cheek we found exceedingly high levels of transepidermal water loss (TEWL) as compared to those in the normal skin of healthy subjects. However, it is not clear whether the skin of patients with AD also shows an abnormally slow recovery after mechanical damage. We compared the recovery of the barrier function of the stratum corneum (SC). after its complete removal by tape stripping, in patients with AD and age‐matched healthy control subjects. On the normal‐looking skin of the flexor forearm, we found no difference in the recovery process of the water barrier function of the SC between the two groups. This suggests that ability to reconstruct SC barrier function after mechanical damage is not impaired in AD patients.

Acrokeratosis paraneoplastica (Bazex syndrome) associated with primary cutaneous squamous cell carcinoma of the lower leg, vitiligo and alopecia areata

We report a case of acrokeratosis paraneoplastica (AP; Bazex syndrome), characterized by typical palmoplantar hyperkeratosis and psoriasiform scaly erythema of the acral regions, associated with primary cutaneous squamous cell carcinoma (SCC) on the left lower leg. This 54‐year‐old Japanese man subsequently developed vitiligo, and alopecia areata of the scalp. Serial monitoring of squamous cell carcinoma antigen (SCC‐Ag) demonstrated that the severity of the clinical manifestations of AP paralleled the serum concentrations of SCC‐Ag. We suggest that an immune‐mediated mechanism underlies the development of AP in this patient.

Reduced proliferative responses of peripheral blood mononuclear cells specifically toCandida albicans antigen in patients with atopic dermatitis — comparison with their normal reactivity to bacterial superantigens

Although reduced cutaneous reactivities toCandida, albicans have been reported in patients with atopic dermatitis (AD), there is still controversy as to whether the in vivo lymphocyte proliferation response is normal or reduced. We have also reported that patients with AD manifest a decreased cutaneous response only toC. albicans antigen in scarification patch tests. The purpose of this study was to examine whether patients with AD show normal lymphocyte transformation responses toC. albicans antigen. Peripheral blood leucocytes (PBL) from 21 patients with AD and 14 healthy control (HC) subjects were cocultured with optimal concentrations ofC. albicans antigen and of superantigens (staphylococcal enterotoxin A and B). PBL from the patients with AD showed a significantly lower response toC. albicans antigen, but there was no statistically significant difference, in PBL responses to superantigens between the patients with AD and the HC subjects. This decreased proliferative response of PBL was particularly noticeable in those whose RAST scores forC. albicans antigen were high. These results suggest the development of a specific anergy toC. albicans antigen in patients with AD.

Cutaneous late phase reaction in adult atopic dermatitis patients with high serum IgE antibody to Dermatophagoides farinae: correlation with IL-5 production by allergen-stimulated peripheral blood mononuclear cells

It is known that, in patients of allergic asthma and rhinitis, the late-phase reaction (LPR) occurs 6-12 h after allergen challenge, but there are few reports concerning cytokine production in the cutaneous LPR in atopic dermatitis (AD). We report here the results of our study on the relationship between the cutaneous LPR and the production of cytokines such as IL-4, IL-5, IL-2 and IFN-gamma by peripheral blood mononuclear cells (PBMC) of AD patients. We selected 29 pure AD patients with no history of atopic airway diseases who showed high serum IgE antibody against Dermatophagoides farinae and performed skin prick testing with three different antigens and observed the resultant cutaneous reactions in 23 of the AD patients. Furthermore, we measured the cytokine production by the cultured PBMC under the stimulation of the antigens and compared it with the results of the skin tests. 13 (57%) of these 23 AD patients demonstrated positive LPR in response to D. farinae, and the mean concentration of IL-5 produced by PBMC was higher in these LPR-positive AD patients compared to the LPR-negative ones. Additionally, we noticed that there was a positive correlation between the mean diameter of the erythema of LPR and the level of IL-5 production by PBMC in the LPR-positive patients. We suggest that there are at least two groups in AD patients, i.e. LPR-positive and LPR-negative ones. The observation of LPR can be an important and practical way to classify AD patients into subgroups, which may enable us to regard IL-5 or eosinophils as a target for treatment.

Coexistence of xeroderma pigmentosum with sarcoidosis and adenocarcinoma of the digestive organs.

Xeroderma pigmentosum has not been reported in association with any specific diseases except for skin malignancy. We observed a case of its coexistence with sarcoidosis and adenocarcinoma of the digestive organs, which has been reported only once in the past. A 54-year-old Japanese female with a variant type of xeroderma pigmentosum developed successively multiple lesions of basal cell carcinoma and squamous cell carcinoma on her face. Intensive metastasis studies led to the incidental detection of non-caseating epithelioid cell granulomas in one of the palpable right supraclavicular lymph nodes. Similar granulomas were also revealed in the excised tissue specimen of squamous cell carcinomas of her left cheek. She was also found to have bilateral hilar lymphadenopathy and chronic uveitis. Three years later, she died of colon adenocarcinoma and its liver metastasis.

Linear cutaneous neurilemmomas on the forehead

A 35‐year‐old woman had had pruritic linearly arranged papules on the right side of her forehead for 17 years. A biopsy specimen from one of the papules showed the histopathological appearance of an intradermal plexiform neurilemmoma. No other features of systemic neurofibromatosis or neurilemmomatosis were detected. Neurilemmoma usually occurs as a solitary lesion in the subcutis and there are only few reports of such localized multiple intradermal neurilemmomas associated with neither neurofibromatosis nor neurilemmomatosis.