Porokeratosis: An enigma beginning to unravel

Porokeratosis is a keratinization disorder with unclear etiopathogenesis, varied clinical presentation and characteristic histopathology, and is usually unresponsive to current therapeutic options. Until now, it was considered to be a clonal disorder with immunity, ultra violet radiation and other factors playing important roles in etiopathogenesis. It is now known that abnormalities in the mevalonate pathway are responsible for this clonal keratinization abnormality. New variants of porokeratosis like eruptive bullous, pruriginous, lichen planus like, follicular variants and porokeratoma have been described. While the cornoid lamella is the classical histopathologic feature, dermoscopy and reflectance confocal microscopy make the diagnosis clearer. Development of malignancy in a few variants is a concern. Linear, disseminated superficial actinic and giant lesions are most prone to developing malignancies. Bowen’s disease, squamous cell carcinoma, basal cell carcinoma and even melanoma have been reported in cases of long-standing porokeratosis. Newer modalities of therapy such as photodynamic therapy, ingenol mebutate and HMGCoA inhibitors may play a role in the future

A rare case of scrub typhus vasculitis presenting as acute coronary syndrome diagnosed by skin manifestations

A 48-year-old diabetic man presented with complaints of acute onset chest heaviness with palpitations, anxiety and headache. He had raised troponin-T level and electrocardiogram showed ST elevation myocardial infarction. There was a prior history of fever of 4 days duration with associated abdominal pain. He later developed skin rash and neurological symptoms following admission to the hospital. Dermatological examination revealed purpura and a livedo-like rash. Investigations revealed deranged liver and renal function tests and positive serological tests for scrub typhus. Coronary angiography revealed no evidence of atherosclerosis or any other pathology. He was therefore diagnosed as a case of scrub typhus-induced vasculitis with coronary manifestations and was managed with oral doxycycline. Scrub typhus presenting like an acute coronary syndrome has been reported very rarely previously. In addition, patient had gastrointestinal, central nervous system and hematological involvement which added to the rarity of the case.

Unconventional treatment options in psoriasis: A review

Psoriasis is a common skin disease that affects 1–3% of the general population. The treatment depends on body surface area involved, quality of life impairment and associated comorbidities. The treatment options include topical therapy, phototherapy, conventional systemic therapy (methotrexate, cyclosporine and acitretin), biologics and oral small molecules (apremilast and tofacitinib). Despite the availability of newer therapies such as biologics and oral small molecules, many a time, there is a paucity of treatment options due to the chronic nature of the disease, end-organ toxicity of the conventional drugs or high cost of newer drugs. In these scenarios, unconventional treatment options may be utilized as stand-alone or adjuvant therapy. In this review, we have discussed these uncommonly used treatment options in the management of psoriasis.

Livedoid vasculopathy: A review of pathogenesis and principles of management.

Livedoid vasculopathy is a rare cutaneous disease manifesting as recurrent ulcers on the lower extremities. The ulceration results in atrophic, porcelain white scars termed as atrophie blanche. The pathogenesis is yet to be understood with the main mechanism being hypercoagulability and infl ammation playing a secondary role. The important procoagulant factors include protein C and S defi ciency, factor V Leiden mutation, antithrombin III defi ciency, prothrombin gene mutation and hyperhomocysteinemia. Histopathology of livedoid vasculopathy is characterized by intraluminal thrombosis, proliferation of the endothelium and segmental hyalinization of dermal vessels. The treatment is multipronged with anti-thrombotic measures such as anti-platelet drugs, systemic anticoagulants and fi brinolytic therapy taking precedence over anti-infl ammatory agents. Colchicine, hydroxychloroquine, vasodilators, intravenous immunoglobulin, folic acid, immunosuppressive therapy and supportive measures are also of some benefi t. A multidisciplinary approach would go a long way in the management of these patients resulting in relief from pain and physical as well as psychological scarring.

A morphometric and immunohistochemical study of melanocytes in periorbital hyperpigmentation.

Background: An increase in number of melanocytes in the basal cell layer of the epidermis is an important feature in many disorders of hyperpigmentation. In this study, we attempted an objective evaluation of the linear density of melanocytes and keratinocytes, along with other epidermal characteristics, in periorbital hyperpigmentation using immunohistochemistry and morphometric techniques. Methods: Melanocytes and epidermal parameters were assessed by digital morphometry in 30 newly diagnosed cases of periorbital hyperpigmentation and 14 controls from the post-auricular region. Melanocytes were labelled with the immunohistochemical stains, Melan-A and tyrosinase. We studied the linear keratinocyte density, mean linear melanocyte density, ratio of melanocytes to keratinocytes, the ratio between inner and outer epidermal length, maximum epidermal thickness and minimum epidermal thickness. Results: Melan-A expression of melanocytes showed strong positive correlation (r = 0.883) with the tyrosinase expression. Mean linear melanocyte density was 24/mm (range: 13–30/ mm) in cases and 17/mm (13–21/mm) in controls and this difference was statistically signifi cant (P < 0.001). The mean ratio of melanocyte to keratinocyte was 0.22 (0.12– 0.29) in cases and 0.16 (0.12–0.21) in controls; again, this difference was statistically signifi cant (P < 0.001). There was a mild negative correlation with linear keratinocyte density (r = −0.302) and the ratio between inner and outer epidermal length (r = −0.456). However, there were no differences in epidermal thicknesses. Limitations: There were fewer control biopsies than optimal, and they were not taken from the uninvolved periorbital region. Conclusion: Mean linear melanocyte density and the ratio of melanocytes to keratinocytes is increased in cases with periorbital hyperpigmentation. It is, therefore, likely that increased melanocyte density may be the key factor in the pathogenesis of periorbital hyperpigmentation.

Expression of apoptosis regulating proteins p53 and bcl‑2 in psoriasis.

Background: Dysfunctional apoptosis has an important role in the development of several skin diseases. Psoriatic keratinocytes possess an enhanced ability to resist apoptosis, which might be one of the key pathogenetic mechanisms in psoriasis. P53 and bcl‑2 are two proteins which control apoptosis. Several studies have evaluated the expression of these two proteins in the psoriatic skin, but the results are controversial. Methods: Fifty‑eight cases of psoriatic skin biopsies were studied, and the grade of p53 and bcl‑2 immunostaining was correlated with the histopathological indices of severity. Results: Bcl‑2 expression in the epidermis strongly correlated with the expression in the basal cells and lymphocytes (P – 0.001 and 0.035). There was no correlation with epidermal hyperplasia or with p53 expression in the three compartments. Bcl‑2 expression in the basal layer correlated with the p53 expression in the epidermis (P – 0.027), basal layer (P – 0.015) and the lymphocytes (P – 0.034). There was a strong correlation among the p53 expression in all the compartments. There was also a weak correlation of the p53 expression in the epidermis with the epidermal hyperplasia (P – 0.042). Conclusions: Bcl‑2 does not appear to play an important role in the apoptotic process in psoriasis. In contrast, it is likely that p53 has a far more important role to play. Mutation analysis of the p53 protein is necessary to evaluate if the protein has mutated or if it is of the wild type.

Expression of tumor necrosis factor-α and nuclear factor-kappaB/RelA and the pathogenesis of psoriasis.

Context: Tumor necrosis factor-α (TNF-α) is an important mediator in the pathogenesis of psoriasis. Nuclear factor-kappaB (NF-κB) is a transcription factor that regulates the activity of the proinfl ammatory genes. Psoriasis is an infl ammatory disease and the role of TNF-α and NF-κB, should be considerable. Aims: We studied the role of TNF-α and NF-κB in psoriasis. Materials and Methods: A total of 61 cases of psoriatic skin biopsies were studies and the grade of TNF-α and NF-κB, staining was correlated with the histopathological indices of severity. Statistical Analysis Used: Pearson’s correlation coeffi cient and Chi-square test. Statistical Package for Social Sciences version 13 was used. Results: The TNF-α immunostain in the cytoplasm of the epidermal cells and basal cells showed a strong inverse correlation with the grade of epidermal hyperplasia (P –0.019 and P –0.009, respectively). The epidermal cytoplasmic positivity and lymphocyte positivity for TNF-α did not correlate with the grade of NF-κB immunostaining in the epidermal cell nuclei, basal cells or lymphocytes. The basal cell cytoplasmic positivity for TNF-α correlated with the grade of NF-κB immunostaining in the nucleus of basal cells at a P – 0.005. There was a strong correlation between the epidermal cytoplasmic TNF-α immunostaining with the lymphocyte immunostaining (P –0.08); however, there was no correlation between the TNF-α expression in the other two locations. Conclusions: The study outlines the relationship between NF-κB and TNF-α and their combined role in the development of the characteristic histopathological changes in psoriasis. We hypothesize that NF-κB is involved in stimulating the release of TNF-α which would account for the characteristic histopathological changes of psoriasis. However, it is likely that NF-κB can act independently of TNF-α also in the pathogenesis of psoriasis.

Morphometric study of microvessels, epidermal characteristics and inflammation in psoriasis vulgaris with their correlations.

Background: Vascular proliferation, inflammation and epidermal changes are important features in the pathogenesis of psoriasis. Aims: In this study we attempted an objective evaluation of these parameters using morphometry. Methods: Inflammation, microvessels and epidermal parameters were assessed in 50 newly diagnosed cases of psoriasis vulgaris (between 01 Nov 2008 and 31 Oct 2011) by morphometry. Parameters studied were microvessel density, microvessel caliber, inflammatory cell density in dermis, ratio between inner and outer epidermal length, maximum epidermal thickness, minimum epidermal thickness and difference between maximum epidermal thickness and minimum epidermal thickness. Results: Microvessel caliber showed moderate correlation (r = 0.645) and microvessel density, weak correlation (r = 0.226) with inflammatory cell density in dermis. Both these parameters also showed mild positive correlation with "ratio between inner and outer epidermal length". All parameters except minimum epidermal thickness showed mild positive correlation with inflammatory cell density in dermis. Conclusion: All microvessels and epidermal parameters showed positive correlation with dermal inflammation; and epidermal parameters exhibited positive correlation with micro-vascular dilation. It is likely that inflammation is a key factor in the pathogenesis of psoriasis.

Tuberous sclerosis with portal vein thrombosis, protein C and S deficiency.

A 29-year-old lady with a bad obstetric history and portal vein thrombosis, presented to the Skin OPD for facial lesions. On examination, angiofibromas on face, shagreen patch and periungual fibromas were observed. She also had dental pits and a retinal hamartoma. Investigations revealed hamartomas in the brain and kidney. Hematological work-up showed protein C and S deficiency with Factor V Leiden positivity. Except for the cutaneous symptoms, the patient did not have any clinical manifestations in other organs affected by tuberous sclerosis. A similar association of tuberous sclerosis with protein C deficiency has been reported in only one case in literature.