DIFFUSE PLANE XANTHOMATOSIS IN A PATIENT WITH BUDD-CHIARI SYNDROME AND MONOCLONAL GAMMOPATHY

Diffuse plane xanthomas are characterized by the presence of yellowish plaques on the eyelids, neck, upper trunk, buttocks, and flexural folds. Histology shows foamy histiocytes in the dermis. Approximately half of the cases are associated with lymphoproliferative disorders. Budd-Chiari syndrome is an uncommon condition induced by thrombotic or nonthrombotic obstruction of hepatic venous outflow. We present a case of diffuse plane xanthoma in a 62-year-old man who developed normolipemic plane xanthomas coinciding with Budd-Chiari syndrome and monoclonal gammopathy. We review the English-language literature regarding the rare association of xanthomas and Budd-Chiari syndrome.     

MUCOCUTANEOUS CHANGES IN TUBEROUS SCLEROSIS COMPLEX: A CLINICAL PROFILE OF 27 INDIAN PATIENTS

Background:

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease resulting in a wide array of clinical manifestations, primarily affecting the skin and central nervous system. Mucocutaneous features play a very important role in the recognition of this syndrome.

Aims:

To review the prevalence and patterns of cutaneous manifestations in tuberous sclerosis, in a group of patients from eastern India.

Methods:

Observational clinical study on twenty-seven consecutive patients of tuberous sclerosis collected during a period of four years.

Results:

Most were between 10–20 years of age; the male to female ratio was 2:1. Family history was found in two-thirds. The classical triad of tuberous sclerosis was present in only nine (33.3%) patients. Adenoma sebaceum was the most common cutaneous feature (100%), followed by hypomelanotic macules (92.6%), connective tissue nevi (66.6%), and Koenen''s tumors (33.3%). Oral mucosal fibromas were seen in six (22.22%) patients. Fibromatous plaque over forehead and scalp was seen in three patients. Limitation of the study was small size of study sample.

Conclusion:

Prominent mucocutaneous changes are extremely common manifestation of TSC, which may provide crucial diagnostic clues for primary care physicians.     

家族性高胆固醇血症性黄瘤病1例

报告１例家族性高胆固醇血症性黄瘤病。患者有结节性黄瘤及角膜环。血浆胆固醇和人工密度脂蛋白升高，甘油三酯正常。其两个堂姊妹亦有皮肤黄瘤，尾骨处结节组织病理显示大量的黄瘤细胞和纤维增生。     

睑黄瘤、多发结节性黄瘤并发高脂蛋白血症1例

报告1例睑黄瘤、多发结节性黄瘤并发高脂蛋白血症。患者男,23岁,双眼内眦、两臀部、双肘及膝关节黄色斑疹及结节1年余。实验室检查示:低密度脂蛋白、胆固醇和甘油三酯均增高。皮损组织病理示:真皮层内泡沫细胞和组织细胞。     

Facial Angiofibromas of Tuberous Sclerosis Treated with Topical Sirolimus in an Indian Patient

Facial angiofibromas are the most visible and unsightly of all the cutaneous manifestations of tuberous sclerosis (TSC). A 17-year-old female, a known case of TSC, presented for the treatment of cosmetically disfiguring facial angiofibromas. She was started on twice daily application of 0.1% sirolimus ointment prepared from crushed tablets of sirolimus compounded in white soft paraffin. After 3 months of use, there was visible decrease in the erythema and the size of the angiofibromas. In an attempt to accelerate the response, the concentration was further increased to 1% sirolimus which was used for a month, resulting in a decrease not only in the size and redness but also in the number of the angiofibromas. The patient did not experience any cutaneous or systemic complications related to therapy. Sirolimus belongs to a novel class of anticancer drugs known as mTOR (mammalian target of Rapamycin) inhibitors. Sirolimus has been used as a targeted therapy for the renal and neurological manifestations of TSC. Topical preparation of sirolimus is not commercially available till date and hence preparations from crushed tablets or oral solution of sirolimus have been used with beneficial effects in treatment of angiofibromas especially in younger patients with flatter lesions. Randomized controlled trials are necessary to enable us to confirm the efficacy, long-term safety, the optimal dosage and possibility of reappearance once the drug is withdrawn. This is possibly the first case report of the use of topical sirolimus in India.     

Epidermolysis bullosa acquisita with moderately severe Dysphagia due to esophageal strictures

Epidermolysis bullosa acquisita (EBA) is a chronic, autoimmune condition involving the skin and mucous membranes. Symptomatic mucosal involvement is rare, but can impact on quality of life, due to esophageal strictures and dysphagia. We report a case involving a 60-year-old male presenting with bullous skin lesions on areas of friction on his hands, feet and mouth. Milia were visible on some healed areas. Biopsy showed a subepidermal vesicle. Direct immunofluorescence showed intense linear junctional IgG and C3 at the dermo-epidermal junction. Serological tests also supported the diagnosis of EBA. Screening tests for underlying malignancies were negative. Despite treatment with systemic steroids, the patient developed increasing dysphagia, requiring further investigation with esophagoscopy and a barium swallow. Confirmation of extensive esophageal stricturing prompted adjustment of medications including an increase in systemic steroids and addition of azathioprine. Currently, the patient's disease remains under control, with improvement in all his symptoms and return of anti-basement membrane antibody levels to normal, whilst he remains on azathioprine 150 mg daily and prednisolone 5 mg daily. This case highlights the fact that the treatment of a given patient with EBA depends on severity of disease and co-morbid symptoms. Newer immunoglobulin and biological therapies have shown promise in treatment resistant disease. Considering that long-term immunosuppressants or biologicals will be required, potential side effects of the drugs should be considered. If further deterioration occurs in this patient, cyclosporin A or intravenous immunoglobulin (IV Ig) will be considered. Vigilance for associated co-morbidities, especially malignancies, should always be maintained.     

Sitosterol xanthomatosis

BACKGROUND: Sitosterolaemia is a lipid disorder in which plasma plant sterol levels are extremely elevated. Sitosterolaemia is clinically characterized by tuberous and tendon xanthomas, premature vascular disease and arthritis. OBJECTIVE: To report a case of sitosterolaemia diagnosed by cutaneous manifestations and to review this rare disease. METHODS: We report the case of a 60-year-old woman who presented with cutaneous xanthomas, arterial hypertension and polyarthralgias. The patient had had hypercholesterolaemia for many years without reduction of serum cholesterol, despite treatment with fenofibrate. RESULTS: Ezetimibe therapy was started, decreasing sitosterol plasmatic levels and tuberous xanthomas after 3 months of treatment. CONCLUSION: It is important to detect levels of sitosterol in plasma in patients with premature vascular disease, presence of xanthomas, and uncontrolled hypercholesterolaemia. Ezetimibe therapy is effective.     

Leukocytoclastic vasculitis: a window to systemic churg strauss syndrome

A twenty year old male presented with purpuric lesions with chronic painful ulcers over the lower extremities and a recurrent pruritic rash on the trunk for 10 years. He was diagnosed as idiopathic leukocytoclastic vasculitis (LCV) after investigations failed to reveal a systemic association. He was treated with immunosuppressants at each visit with partial remission. In 2004, he was diagnosed with bronchial asthma and allergic rhinitis. In his recent admission, he showed necrotic ulcers on legs and extensive shiny, truncal micropapules. Examination revealed maxillary sinus tenderness and loss of sensation on the medial aspect of the left lower limb. Biopsy of ulcer and the micropapules showed the presence of extravascular eosinophils, while hematological investigations showed peripheral eosinophilia of 18%, raised serum Immunoglobulin E (IgE), Anti nuclear antibody (ANA) positivity and negative antineutrophil cytoplasmic antibody (ANCA). Radiography confirmed maxillary sinusitis, nerve conduction studies revealed mononeuritis of the anterior tibial nerve and pulmonary function tests (PFT) were normal. Clinical examination and investigations pointed towards the diagnosis of Churg-Strauss syndrome (CSS). This report highlights the development of full-blown CSS over a period of 12 years in a patient initially diagnosed as idiopathic LCV, emphasizing the need for regular follow-up of resistant and recurrent cases of LCV.     

Tuberous xanthomas in sitosterolemia

Sitosterolemia is an autosomal recessive lipid disorder in which plasma plant sterol levels are extremely elevated and cholesterol levels are often elevated but may be normal. Clinically sitosterolemia is characterized by xanthomas, premature vascular disease, and arthritis. Adolescent boys and girls with sitosterolemia are susceptible to fatal cardiac events. Dermatologists may have a vital role in the diagnosis of this rare but serious condition because early detection and treatment are important in preventing the associated atherosclerotic heart disease. We present a 7-year-old girl with sitosterolemia and tuberous xanthomas.     

A Rare Case of Plantar Epithelioma Cuniculatum Arising from a Wart

A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right-sided hemiplegia, came with the chief complaints of a large cauliflower like growth with pus discharge on the left heel since 15 years. The patient had sustained a penetrating injury by a thorn on the left heel region few days before the lesion appeared. Dermatological examination revealed a single verrucous lesion measuring 7 × 7 cm on the left heel region associated with discharge of foul smelling cheesy material. There was also a enlarged right inguinal lymph node which was non-tender, firm, measuring 2 cm in diameter with normal overlying skin. X-ray left ankle was done which showed some soft tissue swelling. A skin biopsy showed hyperkeratosis, acanthosis and parakeratosis. Elongated rete ridges with keratinocyte hyperplasia, forming a large mass pressing on the underlying dermis were seen. There was formation of multiple large keratin filled invaginations and crypts. No atypical cells were seen. Based on history, clinical examination and investigations, a diagnosis of epithelium cuniculatum type of verrucous squamous cell carcinoma was made. A wide excision with a flap cover was performed in consultation with the oncosurgeon and the excision sample was sent for histopathological re-examination, which confirmed the diagnosis of epithelioma cuniculatum.     

Role of In Vivo Reflectance Confocal Microscopy in Determining Stability in Vitiligo: A Preliminary Study

Background:

Vitiligo is an acquired pigmentary disorder. In vivo reflectance confocal microscopy (RCM) reproducible imaging technique has already been reported to be useful in the diagnosis of other skin diseases.

Objective:

To define RCM features of vitiligo on different clinical stages.

Materials and Methods:

A total of 125 patients with a clinical diagnosis of vitiligo were included in this study. After informed consent, lesional skins of those vitiligo patients were characterized by using RCM. Five patients with inflammatory cell infiltration observed at the edge of skin lesions and another 5 patients without inflammatory cell infiltration were selected. Biopsies were performed at same sites of the RCM examination areas for histological and immune-histological analysis.

Results:

In the active stage of vitiligo, the RCM examination revealed that the bright dermal papillary rings presented at the dermoepidermal junction level in normal skin lost their integrity or totally disappeared, border between vitiligo lesion and normal skin became unclear, and highly refractile cells that referred to infiltrated inflammatory cells could be seen within the papillary dermis at the edge of the lesions. In the stable stage of vitiligo, the RCM showed a complete loss of melanin in lesional skin and a clear border between lesional and normal skin.

Conclusion:

A simple clinical examination with RCM may reliably and efficiently allow evaluation of the stability status of vitiligo lesions.     

Zinc-responsive acral hyperkeratotic dermatosis—A novel entity or a subset of some well-known dermatosis?

Background:

We are reporting a series of interesting cases, which presented to us with psoriasiform lesions distributed over the acral regions of the body. The cases are unusual because they were resistant to conventional treatment modalities like topical corticosteroids, tacrolimus and oral methotrexate but showed significant improvement on oral zinc therapy.

Materials and Methods:

Ten patients with characteristic clinical features of distinctive hyperkeratotic plaque in the acral areas, who were resistant to treatment by different modalities including potent topical steroids and oral methotrexate, were included for detailed investigations. A proper history was taken and relevant laboratory investigations were done which included blood count, urine, liver function, renal function, hepatitis-C virus serology and serum zinc levels. Patients were followed up every 2 weeks. Histopathological examinations of the lesional tissue were done at baseline and after 6 weeks of therapy. Patients were given oral zinc daily and no other treatment during the 6 weeks course.

Results:

All our patients were non-reactive to hepatitis-C. Of the ten patients only one patient (10%) showed low titer of serum zinc, another (10%) showed higher zinc level, while the rest of the patients had normal zinc level. Five of our patients had chronic renal failure, one had Grave''s disease and the remaining had no associated systemic illness. Histopathology mostly showed hyperkeratosis, acanthosis, prominent granular layer, spongiosis and dermal infiltrate. After 6 weeks of follow up, all patients showed rapid and remarkable therapeutic response with zinc.

Conclusions:

We here report a series of patients, discernible because of their uniform clinical presentation of acral hypekeratotic plaques and in showing a noticeable response to zinc. Clinical, histopathological and laboratory investigations were done to rule out diseases of similar morphology including psoriasis, acral necrolytic erythema and lichen simplex chronicus. Authors understand that further studies with greater number cases and more detailed investigations are required to establish exact etio-pathogenesis and nomenclature of this distinct subset of patients.     

Familial homozygous hypercholesterolemia: report of two patients and review of the literature

Familial homozygous hypercholesterolemia is a rare autosomal dominant, metabolic disorder caused by mutation in the gene, which encodes the synthesis of low-density lipoprotein receptors and is characterized by increased serum low-density lipoprotein cholesterol. Multiple types of xanthomas occur, such as tendinous, tuberous, xanthelasma, and sub-periosteal. Intertriginous xanthomas are rare but if present are pathognomonic of this disorder. We report two children with familial homozygous hypercholesterolemia who had multiple xanthomas including the intertriginous variety.     

The Evaluation of the Impact of Age,Skin Tags,Metabolic Syndrome,Body Mass Index,and Smoking on Homocysteine,Endothelin-1, High-sensitive C-reactive Protein,and on the Heart

Background:

Skin tags (STs) are small, pedunculated skin-colored or brown papules that occur around any site where skin folds occur. The literature is short of comprehensive and controlled clinical studies aimed to evaluate the atherogenic risk factors in patients with STs.

Aim of Work:

The aim of this study is to evaluate the impact of age, STs, metabolic syndrome (METs), body mass index (BMI), and smoking on homocysteine (Hcy), endothelin-1 (ET-1), high-sensitive C-reactive protein (Hs-CRP), and on cardiovascular diseases.

Materials and Methods:

This study included 30 cardiac patients with STs, 30 non-cardiac patients with STs, and 30 healthy controls with neither heart disease nor STs. History of smoking, measurement of height, weight, BMI, waist circumference (WC), blood pressure, STs number, color, acanthosis nigricans, estimation of serum level of fasting glucose, triglycerides (TGs), cholesterol, high-dense lipoproteins (HDL), Hcy, ET-1, Hs-CRP, and the presence of the METs were elicited in the three groups.

Results:

Regarding the Hcy, ET-1, and Hs-CRP, the cardiac-STs group showed the highest levels and the control group showed the least (P < 0.001). The percents of patients with METs were 56.7% in the cardiac-STs, 40% in the non-cardiac-STs, and 0% in the control group (P < 0.001). Mean BMI exceeded the limit of obesity in the cardiac-STs group (30.9 ± 3.9) and the non-cardiac-STs group (32.6 ± 6) and was normal in the control group (24.7 ± 2.8). Hyperpigmented STs were present in 66.7% of the cardiac-STs group. Multivariate regression analysis for the independent effectors on Hcy level were the presence of STs (P < 0.001), METs (P = 0.001), and BMI (P = 0.024). Regarding ET-1, the effectors were the presence of STs and METs (P = 0.032). For Hs-CRP, effectors were the presence of STs (P < 0.001) and smoking (P = 0.040). Multivariate logistic regression of the predictors of cardiac disease showed that the independent predictors of the occurrence of cardiac disease were BMI (P < 0.001), STs (P = 0.002), and METs (P = 0.037).

Conclusion:

STs may act as a physical sign of underlying raised cardiac atherogenic factors. This may indicates an ongoing risk on coronary circulation which may indicate further corrective action, hopefully early enough. The association of ST with obesity and METs represents a Bermuda Triangle that act against the heart.     

Caveolin-1 Expression in Different Types of Psoriatic Lesions: Analysis of 66 Cases

Background:

Caveolin-1 is a key structural and functional protein. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation.

Objectives:

To examine the expression of caveolin-1 in skin biopsies from normal subjects, patients, and subjects with the three respective isoforms of psoriasis (psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis). The expression level of caveolin-1 was compared among psoriasis vulgaris, localized pustular psoriasis, erythrodermic psoriasis, and normal subjects.

Materials and Methods:

Using immunohistochemical methods, caveolin-1 protein expression was assayed in four groups. An analysis was conducted on skin samples obtained from 22 normal subjects and 28 patients with psoriasis vulgaris, 22 patients with localized pustular psoriasis, and 16 patients with erythrodermic psoriasis. The statistical analysis of the scoring criteria reflecting the level of Caveolin-1 immunostaining between different groups was determined using the Mann–Whitney U-test.

Results:

In the normal skin, intense and consistent caveolin-1 staining was present in 22 cases. The Caveolin-1 protein was significantly reduced and showed very weak or absent staining within the tissues of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis (respective P < 0.001). Caveolin-1 protein expression in psoriasis vulgaris was higher than that in localized pustular psoriasis and erythrodermic psoriasis (respective P < 0.05). Caveolin-1 protein expression was no different in localized pustular psoriasis and erythrodermic psoriasis (P > 0.05).

Conclusion:

The finding of this study was consistent with a downregulation of Caveolin-1, which might serve as an etiological factor in the development of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis. Further mechanistic investigations are required to prove that Caveolin-1 protein has the potential and may be a novel target for therapy of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis.     

Expression of apoptosis regulatory markers in the skin of advanced hepatitis-C virus liver patients

Background:

Hepatitis-C virus (HCV) infection is considered a major worldwide public health problem with a global prevalence. Maintenance of skin homeostasis requires a delicate balance between proliferation, differentiation, and apoptosis. Meanwhile, it is unclear if there is an altered keratinocyte proliferation/apoptosis balance in advanced liver disease with HCV infection.

Aim:

This work aimed to evaluate the epidermal thickness and changes in the expression of apoptosis regulatory markers as well as apoptotic index in skin samples of advanced HCV liver patients compared to normal controls.

Materials and Methods:

Twenty biopsies were taken from apparently normal skin of advanced HCV liver disease patients, as well as five healthy control subjects. These specimens were used for histometric epidermal measurement, immunohistochemical staining of apoptosis regulatory proteins (Bax, Fas, p53, Caspase-3, Bcl-2, Bcl-xL) as well as the TUNEL technique for detection of apoptotic cells.

Results:

The mean epidermal thickness was significantly lower than the control group (P=0.000). There were significant overexpression of pro-apoptotic markers (Bax, Fas, P53, and Caspase-3) in patients (P=0.03, 0.03, 0.003, 0.003 respectively), with increased apoptotic index in HCV liver patients (P=0.002) when compared to normal controls. On the other hand, no statistically significant difference were encountered in the expression of antiapoptotic markers (Bcl-2, Bcl-xL) in HCV patients when compared to normal controls (P=0.5, 0.9, respectively).

Conclusion:

These findings suggest that an alteration in the proliferation/apoptosis balance is present in the skin of HCV liver patients.     

Immunomodulatory Mechanisms of Action of Calcitriol in Psoriasis

Background:

Calcitriol is well known for its therapeutic efficacy in psoriasis, but its mechanism of action is still unclear. In this study, we tried to elucidate the precise mechanism of calcitriol for its therapeutic efficacy in psoriasis.

Materials and Methods:

Proliferation and apoptosis studies were done to determine the effect of calcitriol on normal human epidermal keratinocytes (NHEKs) and T lymphocytes. To elucidate the effect of Calcitriol on relevant chemokines and epidermal proteins of psoriasis, real-time polymerase chain reaction were done on the modified reconstructed human epidermis (RHE) an in vitro model of psoriasis. All experiments were done in triplicate. Results were expressed as mean ± standard error of mean.

Results and Conclusions:

In vitro, Calcitriol showed significant inhibition of NHEKs and T lymphocyte proliferation by inducing apoptosis of these cells. Moreover, in an in vitro model of psoriasis (RHE), Calcitriol significantly inhibited relevant gene expression of chemokines (Interleukin-8, Regulated upon Activation Normal T-cell Expressed and Secreted [RANTES]) and psoriasin (S100A7). Here, we observed that Calcitriol inhibits critical pathological events associated with the inflammatory-proliferative cascades of psoriasis. Calcitriol induced apoptosis of NHEKs and T lymphocytes as well as inhibited gene expression of relevant chemokines and epidermal proteins in the in vitro model of psoriasis.     

MULTIPLE SMOOTH MUSCLE HAMARTOMA: CASE REPORT AND REVIEW OF THE LITERATURE

Smooth muscle hamartoma (SMH) is a proliferative disorder of cells originating from muscle cells. It is a benign tumoral mass that usually presents as a single congenital skin-colored and hypertrichotic plaque involving the trunk and extremities. Multiple SMHs have rarely been reported in the literature. We describe the case of a seven-month-old girl with multiple SMHs located over the back and arm areas. The diagnosis was confirmed by biopsy and immunohistochemical (IHC) staining. She had no cerebral or skeletal abnormalities and her growth and development were normal.     

Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous Manifestations

A 37-year-old male presented with severe oral and genital mucosal ulcers, lichenoid eruption and twenty-nail dystrophy. Systemic examination was normal, except for anemia. On investigations, he was found to have persistently elevated peripheral eosinophilia, absolute eosinophil count >5000/mm³, bone marrow showing increased eosinophilic precursors, and infiltration by atypical cells. The serum vitamin B12 levels were grossly elevated, and Philadelphia chromosome study was negative. Thus, a diagnosis of chronic eosinophilic leukemia was made. The patient showed excellent response to imatinib mesylate. We are reporting a rare type of leukemia presenting with predominantly cutaneous manifestations.