Aplasia cutis congenita after exposure to methimazole: a causal relationship?

We report a child with scalp aplasia cutis congenita, whose mother was treated with methimazole during pregnancy. The relationship between antithyroid drug administration during pregnancy and the occurrence of scalp defects is discussed, and the pertinent literature is reviewed.     

Lichen planus with late onset hypogammaglobulinaemia: a causal relationship?

A case of lichen planus of the mouth and vulva associated with late onset hypogammaglobulinaemia, alopecia areata and vitiligo is described, and the possible significance of a B cell defect in the pathogenesis of lichen planus is discussed.     

Pili trianguli et canaliculi is a defect of inner root sheath keratinization: ultrastructural observations of anomalous tonofilament organization in a case

A 4-year-old Caucasian girl with pili trianguli et canaliculi had distinctive findings. These included unique ultrastructural alterations consisting of tonofilament-desmosomal detachment and tonofilament clumping within inner root sheath cells. We believe that the hair anomaly in this condition may be due to a compromised cytoskeleton with subsequent configurational changes of the inner root sheath. Despite these configurational changes keratinization of the inner root sheath occurs. As inner root sheath keratinization typically precedes keratinization of the hair shaft, the abnormally configured inner root sheath determines the surface characteristics of the hair shaft in pili trianguli et canaliculi.     

Oesophageal epidermal naevi as a feature of systematised epidermal naevus syndrome

Systematised epidermal naevi are hamartomas developing from neural ectoderm that can be quite extensive, typically with involvement of the face, neck, scalp, arms, legs and trunk. Involvement of the gastrointestinal tract is rare. We report on a 38‐year‐old Caucasian woman with systematised epidermal naevus syndrome who presented with previously undescribed involvement of the oesophagus, as well as the right side of her scalp, forehead, cheeks, chin, oral mucosa, neck, arms and trunk.     

Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review

The use of checkpoint inhibitors for treatment of advanced malignancies is increasing. Rashes, pruritus, and more rarely, reactions resembling Stevens-Johnsons syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur secondary to checkpoint inhibitors. To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of SJS or TEN associated with checkpoint inhibitors. We identified 18 cases of SJS or TEN-like reactions to checkpoint inhibitors in the literature. There were 12 cases of SJS-like rashes with median time to onset of 5.6 weeks (average of 8.9 weeks), of which five were delayed to week 8 or later from checkpoint inhibitor initiation. The five TEN-like reactions had a median time to onset of 4 weeks (average of 5.38 weeks), of which two were delayed to week 6 or later. SJS/TEN-like reactions to nivolumab (seven cases) had median onset time of 3 weeks, whereas five cases secondary to pembrolizumab had median onset time of 11 weeks. Seven cases in this study described prodromal rashes, which varied from localized papular rashes to generalized morbilliform rashes, prior to evolution into SJS or TEN-like patterns. SJS-like patterns generally improved well on systemic treatment/supportive care and no cases of death were identified, but mortality occurred in three of five patients with TEN-like reactions. Dermatologists should consider the possibility for unique features of SJS/TEN in response to checkpoint inhibitors. Additional studies will be necessary to further characterize SJS/TEN-like eruptions on checkpoint inhibitors and determine the optimal management of these cases.     

Peeling skin syndrome: a clinical., ultrastructural and biochemical study

A case of 'peeling skin syndrome' is reported. We have demonstrated a hitherto unreported keratohyalin abnormality and a four-fold increase of cellular retinoic acid binding protein, in one of two biopsies from an erythematous, scaling lesion.     

Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage

The distribution and persistence of cyclobutane pyrimidine dimers were investigated in mouse skin after chronic and acute exposures to ultraviolet-B radiation. We found that DNA damage accumulated in response to chronic irradiation and persisted in a unique set of epidermal cells located at the basal layer. Treatment with a tumor promoter caused the heavily damaged epidermal cells to divide and p53-immunopositive clusters to form within 24 h suggesting that these cells may be progenitors of the mutant p53 clusters associated with actinic keratoses and squamous cell carcinomas. In contrast to low fluence chronic irradiation, daily treatment with a higher fluence of ultraviolet-B produced extensive hyperplasia and considerably reduced penetration of photodamage. Exposure of chronically irradiated skin to an acute "sunburn dose" of ultraviolet-B also produced significant epidermal hyperplasia and resulted in complete loss of heavily damaged basal cells within 4 d postirradiation. The occurrence and distribution of cyclobutane dimers in human skin correlated well with putative sunlight exposure and resembled that observed in ultraviolet-B-irradiated mice. Heavily damaged basal cells were observed at various sites, including those receiving sporadic sunlight exposure, suggesting that these cells may play an important role in carcinoma formation in humans.     

Morphological alterations of epidermal melanocytes in photoageing: an ultrastructural and cytomorphometric study

To examine pathological changes of melanocytes in photodamaged skin, we performed a comparative cytomorphometric analysis and a qualitative observation of melanocytes from sun-exposed and sun-protected facial skin at the electron microscopic level. The characteristic ultrastructural features of melanocytes in photodamaged skin included a statistically significant increase in their number, a marked nuclear heterogeneity, signs of cell activation, close apposition to photodamaged degenerate keratinocytes, degenerative changes represented by large intracytoplasmic vacuoles, and frequent direct contacts with Langerhans cells. Cytomorphometric analysis revealed significant decreases in cell and nuclear sizes, increases in cell and nuclear perimeters accompanied by irregular contours, and higher degrees of nuclear ellipticity in sun-exposed melanocytes. This study demonstrates that there are remarkable differences in the morphology of melanocytes between photoaged and intrinsically aged facial skin, and supports the concept that photoageing processes contribute to cytological alterations in melanocytes.     

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous reactions that are medication-induced in most instances. While the clinical manifestations of SJS and TEN are well-defined, the optimal treatment for these disorders is not. Case reports have shown benefit with the use of a variety of agents including tumor necrosis factor-alpha inhibitors and cyclophosphamide, whereas thalidomide was associated with an increased mortality. Plasmapheresis and cyclosporine have also demonstrated efficacy anecdotally, albeit with an even smaller number of cases in the literature. Most of the reporting has focused on the use of systemic corticosteroids and intravenous immunoglobulin (IVIG) for these severe reactions. The majority of studies analyzing the use of IVIG in the treatment of SJS/TEN show a benefit, though more recent series cast doubt upon this conclusion. The results of these studies are summarized in this present review study.     

Intraepidermal free nerve endings in guinea pigs: their relationship to epidermal keratinocytes

Using transmission electron microscopy, the intraepidermal free nerve endings in the back skin of spotted black and white guinea pigs were examined. Many intraepidermal free nerve endings were present in both the black areas and the white areas. They were located in the spaces between the basal lamina of the epidermis and the cytomembrane of the basal keratinocyte or in the intercellular spaces between the basal keratinocytes, but never beyond the Malphigian layers. Most of them appeared to belong to sensory nerves and some to adrenergic nerves. They seemed to be related intimately to epidermal keratinocytes.     

Cyclic AMP and epidermal cell division. Cyclic alteration of function in the epidermal cell membrane receptor and its relationship to intracellular concentration of cyclic AMP during active DNA synthesis.

The relationship of cyclic AMP to epidermal cell division has been studied in cultured guinea pig epidermal cells. Tritiated thymidine uptake by cultured cells reached a peak the second day after seeding. A significant drop in the concentration of cyclic AMP occurred simultaneously with the increased uptake of tritiated thymidine into DNA. Those cells in which the concentration of cyclic AMP decreased did not respond to external prostaglandin E₁ (PGE₁) stimulation. The response was restored in the cultured cells on the fourth and fifth when intracellular concentration of cyclic AMP started to rise. The results indicate that there is a cyclic alteration of the surface membrane of epidermal cells during active DNA synthesis which may be related to fluctuation in the intracellular concentration of cyclic AMP.     

Livedoid vasculopathy and high levels of lipoprotein (a): response to danazol

Livedoid vasculopathy (LV) is a thrombo occlusive disorder presenting with recurrent painful ulcers of lower extremities. Association of LV with increased level of lipoprotein (a) (LP(a)), a risk factor for cardiovascular disease, has been reported. Danazol has been used with success in the management of LV, but none of the previous studies looked at the correlation between response to the treatment and level of LP(a). The aim of this study was to demonstrate the efficacy of low‐dose danazol in the treatment of LV and its effects on LP(a). We present four cases with LV who were successfully treated with low‐dose danazol, assessing the clinical characteristics and laboratory tests including the level of LP(a). The average age of the patients was 45 years and the mean duration of the disease was 19 years. The treatment regime of danazol 200 mg daily led to complete healing of ulcers and reduction in pain and a 70% (ranging from 52 to 87%) reduction in the level of LP(a). The limitation of this study is “small sample size.” In our patients with LV, low‐dose danazol led to clinical improvement along with significant reduction in the level of LP(a).     

Hermansky-Pudlak syndrome: report of a case with histological, immunohistochemical and ultrastructural findings

We report a 38-year-old female of Puerto Rican descent with Hermansky-Pudlak syndrome and decreased levels of von Wille-brand factor. Histologic and ultrastuctural findings of non-sun-exposed skin showed melanocytes with short dendritic processes and decreased numbers of melanosomes. Ultrastructutal examination of platelets revealed greatly reduced numbers of delta granules. Recognition of this syndrome is important because skin neoplasms, ceroid deposition and hemorrhagic manifestations can be causes of morbidity and of potential death in patients affected with this syndrome.     

Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules.

Skin biopsies and scale samples from nine infants and one fetus affected with harlequin ichthyosis (HI) were obtained from eight families. Epidermal differentiation was examined by morphologic and biochemical criteria and cell culture studies. Two striking abnormalities were identified; first, keratin and filaggrin expression were abnormal and varied between cases, and, second, in all cases lamellar granules were absent or abnormal, and intercellular lamellae within the stratum corneum were absent. Three HI phenotypes were distinguished by variable expression of epidermal structural proteins. Cases were classified by the absence (type 1) or presence (types 2 and 3) of keratins K6 and K16 ("hyperproliferative" keratins) and by the presence of profilaggrin in the interfollicular epidermis (types 1 and 2 only). Profilaggrin is apparently not converted to filaggrin, but it is retained in the scale. The block in profilaggrin processing may be due to an inactive phosphatase. Siblings in two families (presenting with types 1 and 2) showed the same type classification suggesting that expression of the phenotype is consistent within families but differs between families. Cultured HI keratinocytes were normal by phase microscopy, but abnormal by electron microscopy with no lamellar granules and extensive stacking of the upper layers. We conclude that harlequin ichthyosis is a genetically heterogeneous group of disorders with altered lamellar granules, intercellular lipids, and variation in expression and/or processing of structural protein markers of normal epidermal keratinization. Furthermore, the lamellar granule and structural protein defects may be indirectly related via a mechanism involving phosphorylation/dephosphorylation.