Rachel Friedman-Birnbaum

Diabetic dermopathy and internal complications in diabetes mellitus

Background Diabetic dermopathy is the most common cutaneous marker of diabetes mellitus. The relationship of diabetic dermopathy to internal complications of diabetes mellitus, such as nephropathy, retinopathy, and neuropathy, is still unknown.

Papillon‐Lefèvre syndrome: a study of the long‐term clinical course of recurrent pyogenic infections and the effects of etretinate treatment

A family with a clinical variant of Papillon‐Lefèvre syndrome (PLS), associated with recurrent pyogenic infections, has been followed up for more than 20 years. Of the five living siblings, four were treated with etretinate for a period of at least 21 consecutive months. Clinical follow‐up showed that the course of recurrent infections in susceptible PLS patients, although usually more severe in childhood, can be variable and unpredictable. The etretinate therapy resulted in marked improvement of the keratodermas, and was associated with complete remission of the pyodermas on both keratotic and non‐keratotic skin. It is, therefore, suggested that etretinate may have a primary role in the prevention of recurrent pyogenic infections in susceptible PLS patients.

Histological and direct immunofluorescence study of cutaneous hyperreactivity in Behçet's disease

The mechanism of skin hyperreactivity (pathergy) in Behcets disease is unknown. It has been suggested that the response is due to an Arthus‐like reaction. In 18 patients with active Behçets disease, pathergy was induced and the skin biopsied after 24 h. The histological reaction was that of mild to intense round cell infiltration, perivascular in type. Direct immunofluorescence failed in all 18 patients to demonstrate the local presence of immunoglobulins and complement at the site of lesion. A marked increase in the number of mast cells was observed at the site of reaction and scattered throughout the dermis, the role of which is to be further investigated. The study failed to demonstrate a humoral mechanism in the production of the cutaneous hyperreactivity.

Epidemiological study of classic Kaposi’s sarcoma: a retrospective review of 125 cases from Northern Israel

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.

Apoptosis, Fas and Fas‐ligand expression in melanocytic tumors

Impaired regulation of apoptosis is known to be associated with the development of various forms of cancer. Fas binding ro its ligand. Fas ligand (Fas‐L), has been shown to trigger apoptosis in various cell types. Fas‐L is expressed by melanoma cells and has been suggested to play a role in melanoma escape from immune surveillance. In the present study, we assessed apoptotic activity and examined Fas and Fas‐L expression in malignant melanomas, Spitz nevi and ordinary melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick end labeling. Apoptotic activity was found to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi demonstrated, significant levels of apoptosis in the deep parts of the tumor. Fas was found to be expressed by all Spitz nevi, most melanocytic nevi and approximately half of the malignant melanoma specimens. Fas expression was also significantly more pronounced in Spitz nevus cells as compared with, the two other tumors. The anti‐Fas‐L antibody was found to stain all three melanocytic tumors. Staining was shown to be stronger and more frequent in melanoma cells as compared to the nevus cells. Using the Spearman test, no significant correlation between Fas‐L expression in melanoma cells and apoptosis in MM‐infiltrating mononuclear cells was found, suggesting that Fas‐L expression in melanoma cells may not be instrumental in their ability to escape immune mechanisms of defense. In contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may reflect and possibly contribute to their benign nature.

Immunohistochemical study of p53 protein expression in Spitz nevus as compared with other melanocytic lesions.

The accumuluation of p53 protein was studied immunohistochemically on paraffin-embedded sections of 26 Spitz nevi (SNs), 26 primary invasive cutaneous malignant melanomas (MMs), 20 metastases of MM, and 17 ordinary compound nevi (CNs), using monoclonal antibody BP53–12. Positive reactivity was detected in some of the tumor cells in seven (35%) metastatic MMs, all exhibiting strong nuclear staining; eight (31%) primary MMs, of which seven showed strong nuclear staining; two (7%) SNs, of which only one showed strong nuclear staining; and none of the CNs. The frequencies of the positively stained lesions in general, and the strongly positively stained lesions in particular, in the MM and metastatic MM groups were each statistically significantly higher than the respective frequencies in the SN and CN groups. We believe that the immunohistochemical detection of p53 protein with the use of monoclonal antibodies such as BP53–12 on paraffin sections, especially when strong nuclear reactivity is demonstrated, may prove to be an adjunctive tool in the histopathologic differentiation of MM from SN.

Kaposi's sarcoma: retrospective study of 67 cases with the classical form

The records of 67 Israeli patients with classical Kaposis 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.

Familial clustering of classic kaposi sarcoma

It is widely accepted that there is a causal association between Kaposi sarcoma-associated herpesvirus (KSHV) and Kaposi sarcoma (KS). However, the majority of individuals infected with KSHV never develop KS. Here, we present a unique familial case of classic KS, in which the disease occurs in 4 siblings who have no recognized underlying immunodeficiency. We examine risk factors that could play a role in this condition, including KSHV infection, KSHV DNA load, genetic variants of KSHV, infection with additional viruses, interleukin-6-promoter polymorphism, and HLA genotype. We hypothesize that a genetic susceptibility to KS, in combination with KSHV infection, may play an important role in the presented familial case.

Atrichia with papular lesions maps to 8p in the region containing the human hairless gene.

Atrichia with papular lesions (APL) (OMIM 209500) is a hereditary form of alopecia. Hair loss occurs soon after birth and is followed years later by the development of a diffuse papular eruption. Its mode of transmission is still uncertain. A related but clinically distinct form of alopecia, known as alopecia universalis (OMIM 203655), has recently been found to be associated with a mutation in the human hairless gene. The present report describes the largest consanguineous kindred of APL reported to date and provides strong evidence for autosomal recessive inheritance of this rare disorder. On the basis of a linkage analysis of this kindred using six microsatellite markers spanning the human hairless gene region, we found that the APL locus maps to chromosome region 8p12 in a 5 cM interval between marker D8S560 and marker D8S1739. A maximum lodscore of 3.7 was obtained with marker D8S1786, at a recombination fraction of 0. Our results suggest phenotypic variability at the hairless locus although they do not rule out the existence of a gene cluster associated with hair disorders in the same region.

Mal de Meleda keratoderma with pseudoainhum

Pseudoainhum is an infrequent complication in the autosomal‐recessive keratodermas. We describe two related families in which the diagnosis of mal de Meleda keratoderma has been confirmed by mode of inheritance and ultrastructural findings. One family member, a 9‐year‐old girl, developed pseudoainhum which threatened the viability of her little fingers. This responded to treatment with etretinnte. The treatment dilemma posed hy keratoderma‐induced pseudoainhum in children, i.e. the concern over the possible skeletal toxic effects of long‐term etretinate treatment vs, the risks and outcome of surgery, is discussed.