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Background: Adverse drug reactions (ADRs) are common. In the absence of a sufficiently sensitive and specific laboratory test, identification of the culprit drug remains a diagnostic challenge. Patch tests have recently been advocated as a means of detecting drug sensitivity., Objective: To further elucidate the usefulness of patch tests in revealing the causative drugs of cutaneous ADRs (CADRs)., Materials and Methods: We conducted a non-blinded, prospective, controlled clinical trial. Twenty-five patients with a history of CADRs were patch tested, and 25 healthy subjects who had never experienced CADRs served as controls., Results: A morbilliform eruption was the most frequent skin reaction. Patch tests were positive in eight of the 25 patients with CADR (32%). Specifically, five of the 13 patients with morbilliform drug eruption (38.4%) tested positive, as did one of the four patients with erythema multiforme/Stevens-Johnson syndrome (25%), and one of the two patients with the drug reaction with eosinophilia and systemic symptoms syndrome. Antibiotics and anticonvulsants resulted in positive patch tests most often. Patch test sensitivity was 32%, specificity was 92%, and negative and positive predictive values were 57.5% and 80%, respectively. Significant correlation was found between the patch test result and the clinical probability of a CADR according to the imputability score of the drug., Conclusions: Patch testing for drugs causing ADRs shows high specificity rates even though the sensitivity is low. Such tests may therefore be useful in supporting the diagnosis of delayed-type CADRs, particularly when antibiotics or anticonvulsants are involved and the cutaneous reaction is a morbilliform rash., (© 2016 The International Society of Dermatology.)

Background: Hexavalent chromium in cement is a common cause of occupational allergic contact dermatitis (OACD)., Methods: Analysis of patch test data during 1999 to 2013 was done. Patients with cement-induced chromate OACD filled the Dermatology Life Quality Index, graded 1 to 5., Results: Of 4846 consecutive patients who were patch tested, 146 (3%) were chromate-sensitive. Of 46 (31.5%) who presented with chromate OACD, 27 (59%) had cement-induced chromate OACD. The proportion of chromate-sensitive patients with clinically relevant cement exposure increased from 7.7% in 2002 to 2004 to 28.7% in 2011 to 2013 (P = 0.04). The median age of presentation was younger than for other chromate-sensitive patients (32 vs 42 years). Hand eczema (88.9%) was the most frequent clinical presentation. Of the 27 with cement-induced chromate OACD, 21 (77.8%) had ongoing dermatitis at the time of the review. Although 14/27 (51.9%) changed their occupation to avoid exposure to cement, symptoms persisted in 9/14 (64.3%). Prolonged exposure to cement before development of symptoms was associated with chronicity. All the symptomatic patients experienced at least a moderate effect on their quality of life (grade 3 or higher on the Dermatology Life Quality Index)., Conclusions: We recommend the adoption of the European legislation in Israel, to reduce the prevalence of chromate OACD from cement.

Background: The prevalence of chromate allergy has declined worldwide in the last decades., Objectives: The aim of the study was to assess tendencies in chromate allergy in northern Israel and its possible causes., Methods: Retrospective analysis of patch test data during 1999-2013 and a review of the medical records of patients with chromate allergy were conducted., Results: A total of 4846 consecutive patients were patch tested, of whom 146 (3%) were found to be chromate sensitive. The prevalence of chromate allergy decreased significantly from 4.7% in 1999-2001 to 2.8% in 2002-2004 (P = 0.02). Since then, no significant fluctuations have occurred. A gradual and consistent decline in chromate allergy was recorded among women from 4.8% in 1999-2001 to 2.3% in 2008-2010. Cement (18.4%) was the most frequent source of exposure and was mainly observed in men. The frequency of clinically relevant cement exposure increased significantly from 7.7% in 2002-2004 to 28.7% in 2011-2013 (P = 0.04), whereas the frequency of relevant detergent exposure decreased significantly from 25% in 1999-2001 to 5.7% in 2011-2013 (P = 0.04). Hand (68.5%) was the most frequently involved anatomical site., Conclusions: The prevalence of chromate allergy in northern Israel is stable in the general population and gradually decreasing among women. These changes may be caused by reduced exposure to water-soluble hexavalent chromium in detergents but not in cement.

Background: One of the suggested causes of primary cutaneous lymphoproliferative disorders is persistent antigenic stimulation., Objective: To study the prevalence of contact hypersensitivity in patients with primary cutaneous lymphoproliferative disorders other than mycosis fungoides (MF)., Materials and Methods: Thirty consecutive patients with primary cutaneous lymphoproliferative disorders other than MF were patch tested to a European Standard & partial metal series. The results were compared with those of 792 consecutive patients with other skin diseases referred to our clinic and a large published series of 9760 healthy individuals from North America., Results: Twenty-two patients with primary cutaneous lymphoma other than MF and eight patients with pseudolymphomas were included in the study. Altogether there were 23 positive patch tests in 13 patients. Only the prevalence of positive patch tests to cobalt (5/30 patients = 17%) was found to be significantly higher in the studied group than in the two control groups (P<0.01 and P=0.05, respectively). The contact hypersensitivity to cobalt and the other allergens, however, could not be related causally to the pathogenesis of the lesions., Conclusions: The relative prevalence of contact hypersensitivity to cobalt only was found to be increased in a group of primary cutaneous lymphoproliferative disorders, but a causal relationship to the lymphoproliferative disorders could not be established., (© 2011 The International Society of Dermatology.)

The clinical manifestations of contact allergic dermatitis to dental materials are not uniform. This study was performed to detect the frequent allergens in the dental series associated with contact dermatitis and to define the causal relationship between the different allergens and the relevant clinical presentations. Between the years 2000 and 2004, 134 patients, aged 20-80 years, were patch tested. 121 patients were included in the study. The most frequent oral manifestations were cheilitis and perioral dermatitis (25.6%), burning mouth (15.7%), lichenoid reaction (14.0%), and orofacial granulomatosis (10.7%). 18 (14.9%) patients were dental personnel, all of whom suffered from hand dermatitis. The common allergens detected included goldsodiumthiosulphate (14.0%), nickel sulfate (13.2%), mercury (9.9%), palladium chloride (7.4%), cobalt chloride (5.0%), and 2-hydroxyethyl methacrylate (5.8%). Positive reactions to metals were frequent in all the different clinical variants, and no specific association between a specific clinical presentation and a particular allergen was found. Allergy to mercury was not a significant factor contributing to the pathogenesis of oral lichenoid reactions. However, a strong association with contact allergy to mercury in dental fillings was found in 2 patients with orofacial granulomatosis.

This study presents a 10-year survey of 2285 patients tested to common preservatives in northern Israel. The demographic and clinical data were analysed using a revised MOAHLFA index. Patch testing was based on the International Contact Dermatitis Research Group (ICDRG) guidelines. 411 (18%) patients were found to have positive reactions to 1 or more preservatives. The most frequent allergens tested positively were thimerosal, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and formaldehyde. The reactions to MCI/MI remained stable around 1.7% throughout the years 1995-1998, with a significant increase to 3.7%-4% (P = 0.029) during 1999-2004. The reactions to formaldehyde remained low around 0.3% until 1999; however, a considerable increase throughout the years 2000-2004 was noted, with rates of 1.5%-1.9% (P = 0.028). The sensitivity rates for parabens, quaternium-15, imidazolidinylurea, and diazolidinylurea were low and unchanged, mostly under 0.5%. As for methyldibromoglutaronitrile (MDBGN), sensitivity rates around 2% were detected for the years 1996 and throughout 2000-2004. Overall, this extensive survey showed a concerning increase in the sensitivity rates for MCI/MI, formaldehyde, and MDBGN.

A cutaneous eruption simulating insect bites has been repeatedly described in association with chronic lymphocytic leukemia (CLL). It was only rarely described with mantle cell lymphoma (MCL). Our study was performed to elucidate the clinical, histologic, immunopathological, and molecular characteristics of insect bite like reaction (IBLR) associated with MCL. The clinical presentation and histologic findings in 3 IBLR cases associated with MCL were found to be similar to 3 IBLR cases associated with CLL. The eruptions consisted of itchy erythematous papules, nodules, plaques, and vesicles. Non-vesicular lesions were characterized histologically by normal or mildly spongiotic epidermis. Vesicular lesions were characterized by marked spongiosis and intraepidermal spongiotic vesicles containing eosinophils, or marked subepidermal edema occasionally leading to a dermoepidermal separation. Most of the lesions were characterized by superficial and mid dermal to deep perivascular and interstitial, and occasionally periadnexal, inflammatory-cell infiltrate consisting of mononuclear cells and eosinophils. The densities of the infiltrates varied and the inflammatory-cell infiltrate extended often into the fat lobules. Neutrophils and nuclear dust were found more frequently and abundantly in the IBLR lesions associated with MCL. Immunophenotyping, direct immunofluorescence (DIF) tests, and IgH gene rearrangement studies were performed in the lesions associated with MCL only. The majority of the infiltrating lymphocytes were CD3+, CD5+ and CD43+, more CD4+ than CD8+, and only a small minority was CD20+. The cells did not stain for bcl-1 protein and CD30, and with no evidence of clonality. The DIF test result was negative. The IBLR eruption associated with MCL resembles clinically and histologically IBLR associated with CLL. The eruption seems to be reactive rather than neoplastic, because there is no evidence of MCL involvement in the skin lesions.

Background: Indirect immunofluorescence (IIF) is the standard method for the detection of pemphigus autoantibodies. Commercially available enzyme-linked immunosorbent assays (ELISAs) have recently become available to measure serum antibodies (Abs) against desmoglein1 (Dsg1) and desmoglein3 (Dsg3). It has been suggested that patients with mucosal-dominant pemphigus vulgaris (PV) have serum Abs against Dsg3 only, patients with mucocutaneous PV have Abs to both Dsg1 and Dsg3, and patients with pemphigus foliaceus (PF) have Abs against Dsg1 only., Aim: To compare the sensitivity and specificity of the IIF and ELISA tests in the diagnosis of pemphigus and its subsets., Methods: Thirty-three patients with PV and five patients with PF were studied, and compared with 50 healthy individuals or patients with unrelated skin diseases. Monkey esophagus was used as a substrate for the IIF test., Results: The IIF and ELISA tests were each positive in 26 of the 32 (81%) PV patients, and in none (0%) and 3 (6%) of the 50 controls, respectively. Both the IIF and ELISA results were concordant in 69% of the PV patients, and only one of these two tests was positive in the remaining 31% of patients. Forty-six per cent of the PV patients with a positive ELISA test did not have the PV phenotype (mucosal or mucocutaneous) predicted by their autoantibody profile., Conclusion: The IIF and ELISA tests may be used as complementary tests for the serologic diagnosis of pemphigus.

Nevirapine is a non-nucleoside reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV)-infected patients and in post-exposure prophylaxis. However, its use has recently been limited because of adverse cutaneous and hepatic effects. We report an HIV-infected woman who developed mild leukopenia as the first sign of a nevirapine-related adverse event, which was followed by skin and hepatic toxicity associated with a more severe leukopenia.

A 61-year-old woman presented with a 2-year history of an abnormal erythematous swelling on the upper lip and cheek. Upon examination there were no other physical findings. Histological examination found discreet sarcoidal granulomas in the lower dermis. Routine laboratory studies, chest radiographs and pulmonary functions were all normal. Clinical presentation and histological findings were, therefore, compatible with the diagnosis of orofacial granulomatosis (OFG). The patient was patch tested with an extended standard series that included metal-salt, dental prosthesis, bakery and corticosteroids series. The patch test was positive (score ++) after 48 and 72 h for mercury in the metal-salt and dental prosthesis series. During the past decade the patient had received amalgam fillings of several dental cavities, including one adjacent to the swollen cheek. The unilateral localization of the soft tissue swelling adjacent to the amalgam tooth fillings, along with the positive patch test for mercury, raised the possibility that the OFG was part of a delayed hypersensitive reaction to the fillings. The patient therefore underwent a total amalgam replacement procedure; complete disappearance of the swelling overlying the right cheek was observed within 7 weeks and the swelling of the upper lip subsided completely within 6 months. We propose that mercury in amalgam tooth fillings is another cause of OFG and suggest appropriate patch testing in patients who do not have an apparent cause of OFG.

Background: Classical Kaposi sarcoma (CKS) is a rare indolent neoplasm that is particularly prevalent among Jews of Ashkenazi and Mediterranean origin. Data regarding prognostic factors for CKS are scarce. The aim of the current retrospective analysis was to better define prognostic subgroups among patients with CKS., Methods: Between 1960 and 1995, 248 consecutive patients with CKS were treated at the Rambam and Rabin Medical Centers in Israel. Although treatment options included local excision, radiotherapy, and chemotherapy, observation alone was used for 31% of patients. For prognostic factor analysis, disease progression was classified as any progression and dissemination, and progression-free survival was calculated for each., Results: At a median follow-up of 20 months, four patients (1.6%) died of CKS. Of the patients eligible for analysis, 94 of 220 (39%) had any progression and 23 of 120 (18%) had dissemination. Only 8 of 202 (4%) had visceral spread. On univariate analysis, age was a statistically significant prognostic factor for any progression (P = 0.04), whereas immunosuppression and visceral involvement at presentation had only borderline significance. Immunosuppression was the only prognostic factor for dissemination (P = 0.003). On multivariate analysis, both age and immunosuppression were significant prognostic factors for any progression (P = 0.001 and 0.01, respectively). Immunosuppression was also predictive of dissemination (P = 0.006)., Conclusions: Immunosuppression and older age (50 years and older) are strongly associated with poorer outcome among CKS patients. The two end points used in this study may be used for future prognostic factor analyses., (Copyright 2002 American Cancer Society.)

Background: The morphology of Kaposi's sarcoma is clinically and histologically the same in all clinical forms of the disease. However, there is a difference in the clinical and biological behaviour of the different forms of the disease. The behaviour also differs among individuals with the same form. The factors involved in the initiation and prognosis of the disease are still unknown. The classical form is more common in middle-aged Jews of East European or Mediterranean origin, people of Italian and southern Greek origin. Classic Kaposi's Sarcoma is seen relatively more frequently in Israel than in many other countries., Objective: The aim of this study was to examine risk factors that influence the development and course of the disease., Methods: This retrospective study includes 125 patients with Kaposi's sarcoma, all diagnosed and followed in the Department of Dermatology at Rambam Medical Center in Haifa., Results: The group included 85 (68%) men and 40 (32%) women. Fourteen subjects received corticosteroid therapy and three were kidney transplant recipients. Age at onset of the disease was 21-87 years, with a mean age of 67. A total of 121 patients (96.8%) were Jews and four (3.2%) were non-Jews. A majority (61.6%) were of East European origin. The number of new cases each year was constant in relation to the general population, except for two peaks, one in 1970 and another in 1986-89. The lower limbs were involved in most patients. Extracutaneous involvement was present in 18.4%. Of all the subjects, 28 (22.4%) had diabetes mellitus and 21 (16.8%) had a second primary malignancy. The malignancies were of lymphoreticular origin in 10 patients, four in the urinary bladder, three had carcinoma of the large bowel and one of the pancreas., Conclusion: Our study shows similar clinical findings to those described in other series. The relatively high frequency of carcinomas of the colon and urinary bladder was not reported elsewhere. We observed a consistent rate of new cases each year with two peaks in 1970 and 1986-1989, the cause of which deserves explanation. Of interest is the relative rise in the number of females with Kaposi's sarcoma. A relative high risk for developing Kaposi's sarcoma has been found among Jews of Ashkenazi origin compared to those of other ethnic groups. Israeli-born subjects presented a relatively more aggressive course of disease than others.

Recent in vivo investigations have shown that pretreatment with topical all-trans retinoic acid (RA) may diminish the skin response to sodium lauryl sulphate (SLS). This study evaluated the permeation of SLS through human skin after pretreatment with RA, and vice versa, by in vitro methods. The permeability coefficient of SLS (3.24 +/- 0.21 x 10(3) cm/h) and the 24-h cumulative amount of SLS (3.41 +/- 0.6% of dose applied) permeating RA-pretreated skin did not differ significantly from those across untreated skin (control) (P > 0.05). In contrast, the permeability coefficient of RA (0.23 +/- 0.05 x 10(3) cm/h) and its 24-h cumulative amount (0.37 +/- 0.05% of dose applied) penetrating SLS-pretreated skin were significantly greater than those permeating untreated skin (P < 0.05). Thus, an increase in RA penetration was induced by SLS pretreatment; however, pretreating the skin with RA did not inhibit the percutaneous permeation of SLS. Based on previous in vivo findings where RA reduced skin reactions to SLS, one would speculate that RA pretreatment may decrease SLS penetration. However, these penetration data do not necessarily uphold this presumption. Perhaps, other interactions between the substances and the skin, e.g. at cellular levels, may be responsible for the differing skin responses.

Topically applied all-trans retinoic acid (RA) is often associated with skin irritation. A detailed quantification of RA-induced functional changes in stratum corneum is, however, still limited. Using non-invasive bioengineering techniques of measurements of transepidermal water loss (TEWL), stratum corneum hydration and cutaneous blood flow (CBF), we quantified the irritant effects of 0.05% and 0.1% RA in ethanol on normal skin compared with 1% sodium lauryl sulphate (SLS) in water as a model irritant in a 24-h occlusive patch-test assay. Additionally, in order to document data possibly related to the mechanism of action, skin responses to both compounds applied in tandem was also investigated over 18 days. The extent of the irritant response to 0.05 and 0.1% RA, respectively, were similar, implying analogous irritation potency. While RA caused more intense scaling than SLS, other skin responses to RA were significantly weaker than those due to SLS. An increase in TEWL, on day 7, in RA-exposed sites indicates a secondary delayed impairment of the stratum corneum (SC) barrier. In a tandem-design assay, pretreatment with RA appeared to reduce the irritant effects of SLS on SC hydration and CBF. In contrast, pre-exposure to SLS showed a synergestic response in erythema, scaling and TEWL. Our results demonstrate that RA, like SLS, is capable of impairing SC water barrier function, which may be responsible, in part, for the irritation associated with its topical use. However, the distinctive biological responses to these compounds suggest a different mode of action of RA and SLS. In addition, the precise reason for the unique results observed in the tandem-design assays is not clear.

Because of the abundance of the classical form of Kaposi sarcoma (CKS) among Jews and people of Mediterranean origin, studies have been conducted to find an association between CKS and HLA antigens. No conclusive results have been drawn, although in a number of these investigations an increased incidence of HLA-DR5 was reported. In our study 49 CKS patients of Jewish origin were serologically analyzed for HLA class I and class II antigens. We found no significant deviation in serologically defined HLA antigens frequencies between patients and 99 ethnically matched controls. However, a nonsignificant decrease in the frequencies of HLA-DR4, HLA-DR12, and the combination of DR4/DR11 was observed. Then we determined in these patients HLA-DRB1, HLA-DQA1, and DQB1 allelic polymorphism by oligotyping on PCR-amplified DNA. In this molecular analysis the only notable finding was a decreased frequency of the combination HLA-DQA1*0301/DQB1*0301, which appeared in one (2%) patient compared to 13 (13%) of the controls. However, the decrease was not statistically significant. On the basis of both serological and molecular analysis done on a relatively large group of CKS patients, we conclude that there is no significant linkage between HLA antigens and CKS in Jewish population.

The histological findings in the first diagnostic biopsy of 50 patients with Kaposi's sarcoma (KS) were classified and were related to the clinical course. Forty-one patients had the "classic KS," of whom 31 had a benign course and 10 an aggressive disease. Nine patients had iatrogenically induced KS. Histologically the following subtypes were found: mixed type in 18 patients, spindle type in 16, early type in 14, and hemangiomatous and lymphangiomatous types in one each. We did not find any statistical relationship between the histological subtypes, degree of nuclear atypia, number of mitoses, and density of the inflammatory cell infiltrates in the KS lesions, and the clinical types and course of the disease. The results of this study do not support the possibility of a prognostic importance regarding the histological features of the early lesions in patients with classic or iatrogenic Kaposi's sarcoma.

Lymphocyte function as expressed by T-lymphocyte subsets and natural killer cell activity was evaluated in a group of Israeli patients with classic Kaposi's sarcoma. T-cell subsets were examined in 28 patients, 14 with lesions limited to the lower extremities and 14 with diffuse cutaneous or systemic involvement. CD4 and CD8 lymphocytes and CD4/CD8 ratio were in the normal range in all patients, and mean values of the entire group were similar to a control group. However, CD8 was in the upper limits of the normal range in some patients with diffuse cutaneous or systemic involvement. This factor led to a significantly decreased CD4/CD8 ratio in that group as compared with the group of patients with the disease limited to the lower extremities. Mean values of natural killer cell activity in three effector/target cell ratios were significantly decreased in 13 of the patients with Kaposi's sarcoma with lesions limited to the lower extremities and in all of the patients with normal T-cell subsets and CD4/CD8 ratios.

The records of 67 Israeli patients with classical Kaposi's sarcoma treated at Rambam Medical Center were analyzed retrospectively for clinical and laboratory data. As expected, all except 1 patient were of Jewish origin. There was a male predominance with a ratio of 2.2:1. The age of onset was mostly during the 5th to 7th decades of life. The course of the disease was usually slow and indolent. As has been already noted, we found a higher frequency of diabetes mellitus (16.4%). Although a high frequency of second primary malignancy was seen in our patients, this was less so than that described in an American series, 15% as compared to 37%, respectively. The most frequent second malignancy was that of the lymphoreticular system. No serologic evidence for an association with types of herpes virus infection has been found. No alterations in humoral and cellular immunity were demonstrated. These data show similar clinical findings with those described in other series, besides the lower frequency of a second primary malignancy. Some discordance with that described before concerning the relationship with cytomegalovirus infection and T cells subsets was also noted.

Natural killer (NK) cell activity of peripheral blood lymphocytes was evaluated in a group of 13 patients with classical Kaposi's sarcoma (KS). All patients had a normal T4/T8 ratio, and the disease was confined to the skin of the lower extremities. A group of 5 healthy subjects served as controls. NK cell function was significantly decreased in patients as compared to controls. Our result is similar to that found in another group of patients with AIDS-related KS with lymphadenopathy and an abnormal T4/T8 ratio. This suggests that decreased NK cell function is not a result of a progressive process and might be directly involved in the development of KS.

A case of dermal vasculitis with arthralgia after intestinal bypass surgery is reported. A 36-year-old woman developed arthralgia and skin rash, 1 year after an ileo-jejunal bypass operation was performed for overweight (130 kg). Skin biopsy showed leucocytoclastic vasculitis in the dermis. E.M. study showed clumps of platelets around small dermis blood vessels, and polymorphous perivascular infiltration. The symptoms subsided after tetracycline treatment.

A 57-year-old patient with rheumatoid arthritis, who was being treated with D-penicillamine, developed a bullous eruption 2 months after the onset of treatment. On the basis of the clinical, histological and immunofluorescent findings, the diagnosis of herpetiform pemphigus was made. The eruptions disappeared within 2 weeks after the discontinuation of D-penicillamine treatment. During the 16-month follow-up period there was no recurrence. It is noteworthy that a patch test with potassium iodide was positive and that testing for HLA antigens revealed HLA B8, A1, A2, and BW39.

A 29-year-old woman, referred because of the development of diffuse papules and plaques on the face and progressive hair loss, was found to have generalized hair follicle hamartoma, a very rare condition previously described in only two female patients. All three patients also suffered from myasthenia gravis. The histological appearance of both the involved and uninvolved skin was similar to trichoepithelioma.

We have reviewed the morphologic findings in 41 histologic slides of granuloma annulare (GA), 15 from localized (LGA) and 26 from generalized granuloma annulare (GGA). The most common pattern was the histiocytic infiltrative type, more so in cases with LGA than with GGA. The palisading granuloma pattern was present in 21.9% of patients and its prevalence was almost equal in both clinical types. The least prevalent histologic type in all patients taken together was the epithelioid nodule type. However, the prevalence of this type in LGA was equal to that of the palisading type, in contrast to that in GGA where it accounted for only 11.5%. In addition, a mixed histologic pattern was found in greater than 25% of sections from GGA and in only one section from LGA. Periodic acid-Schiff stain revealed hyalinized capillary basement membrane in most of GGA and only in approximately 50% of LGA sections. The variation in prevalence of the different histologic patterns between sections from LGA and GGA, and the difference between our findings and those observed in other series, are discussed.

The histological picture in granuloma annulare (GA) is well defined. The types of infiltrate and the changes in collagen and elastic tissue have been repeatedly described. This is a preliminary study focused on the elastic tissue changes in lesions of generalized GA. Biopsies from four patients were studied. Specimens of involved and uninvolved skin from both exposed and unexposed parts of the body were compared. Changes of actinic elastosis in the papillary dermis in each patient in different stages were observed only in the exposed skin. The typical GA infiltrate was located beneath, in the upper mid-dermis. In the zone of the infiltrate in all specimens--exposed and unexposed--with no regard to the severity of actinic elastotic changes, absence or a marked reduction of elastic material was noted with engulfment of elastic remnants in giant cells. Giant cells with phagocytosis of elastotic material were mostly located on the periphery of the granuloma in the upper as well as in the deeper portion, where elastic fibers were still present. This might support the suggestion that degenerating elastic fibers promote the granulomatous reaction that leads to the formation of granuloma annulare.

Humoral and cellular immunity were evaluated in 10 patients with Darier's disease. The mean levels of serum immunoglobulins, serum complement, peripheral macrophages, and peripheral B and T lymphocytes were within normal limits. Secretory IgA was present in all patients studied. Skin tests for delayed hypersensitivity revealed complete anergy in one of the eight patients tested. Lymphocyte transformation tests revealed statistically significant enhanced responsiveness to both PHA and ConA mitogens in several concentrations studied. These findings may suggest either the existence of alterations in immunoregulation of lymphocyte subpopulations in Darier's disease or may be limited to alterations in membrane functions of certain lymphocyte subpopulations which can be detected only in vitro. The role that such immunologic aberrations may play in the pathogenesis of Darier's disease is still obscure.