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Tuberculosis is a fairly common disease in the United States and around the world, newly infecting ten million people throughout the world per year. Despite the pervasiveness of tuberculosis, cutaneous tuberculosis (CTB) rarely manifests worldwide. Tuberculous infections of the skin arise in several distinct variants that can be classified as either multibacillary or paucibacillary; each subtype within these categories presents with its own morphological and histological findings. The diagnosis of CTB can prove clinically challenging as its variants mimic many conditions dermatologist encounter on a daily basis. Additionally, tissue confirmation is difficult. We report a case of CTB which evolved from a lupus vulgaris presentation to the metastatic tuberculous abscess variant.

Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a variety of etiologies. The conditions may appear as purely orange, yellow-orange, red-orange, tan, or brown with an orange hue. The orange color may also present as a transient phase of a disease process. As with all dermatologic pathology, a key way to distinguish orange-colored lesions is by distribution and morphology. The sclera, palate, lips, gingiva, and nails may also be involved. A literature review using PubMed with keywords, including orange, skin, mucosa, cutaneous, xanthoderma, and granuloma, was conducted to gather all dermatologic conditions that can present with an orange color. The relevant diseases were categorized by etiology and include inflammatory, infectious, neoplastic, and exogenous causes., (Copyright © 2019. Published by Elsevier Inc.)

Skin squamous cell carcinoma is the second most common non-melanoma skin tumor worldwide. Most skin squamous cell carcinoma patients have underlying diseases. Here, we report a 56 year-old patient diagnosed with skin squamous cell carcinoma and with a 30 year course of neglected lupus vulgaris, which was very rare. In this case, we adopted a treatment strategy involving a small wound: superficial resection combined with photodynamic therapy with a satisfied result., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The incidence of all forms of cutaneous tuberculosis, including lupus vulgaris (the most common form) decreased progressively in developed countries during the twentieth century, this change being attributed to improved living standards and specific therapy. Despite the decrease in cutaneous tuberculosis, some cases are still found and correct diagnosis and management are fundamental, both for the patients and for public health. Long lasting, misdiagnosed or untreated cutaneous tuberculosis may lead to different forms of cancer. This case report involves a 74-year old male farmer with lupus vulgaris on his face. During anti-tuberculosis treatment he developed a tumor on his forehead, which was histologically confirmed as a squamous cell carcinoma.

According to current statistics of the WHO, tuberculosis is the infectious disease that causes the most deaths worldwide. Its most common cutaneous manifestation is lupus vulgaris which is seldom diagnosed today. A 69-year old immunocompetent woman complained of a partly elevated, partly sclerotic plaque on her left thigh which had been present for more than 55 years before slowly becoming ulcerated. After biopsy and subsequent excision of the 13 cm ulcer, the diagnosis of carcinoma in lupo with lymph node metastasis was made. Cutaneous and additional nodal metastases appeared rapidly. Tuberculostatic therapy was initiated. Despite systemic chemotherapy the tumor subsequently progressed and the patient died of metastatic carcinoma in lupo 15 months after the initial diagnosis. Early diagnosis and treatment of lupus vulgaris might have prevented the development of carcinoma in lupo and ensuing metastatic death of the patient.

Background: Lupoid cutaneous leishmaniasis (CL) is known as the chronic form of CL. However, keeping its clinical presentation in view, there is a need to revisit this form of disease., Aims: To redefine/describe lupoid CL in view of clinical features., Methods: It was a case series seen in Muzaffarabad (Pakistan) from Jan 2006 to May 2008. All patients clinically suggestive and consistent with laboratory diagnosis of CL were registered. Patients of all age groups and either sex having cutaneous lesions resembling lupus vulgaris or lupus erythematosus on the face or elsewhere were included in the study. Those having chronic fluctuating/relapsing course or scarring within the lesions were also included. Various demographic features of the patients and clinical patterns were recorded. Descriptive statistics were used for analysis., Results: Of 254 registered patients of CL, 16 (6.3%) were diagnosed as lupoid CL. None of the patients had scarred lesions. Age ranged from 38 to 75 (55 + 15.11) years and duration of lesions varied from 4 to 32 (14.25 + 07.59) weeks. All patients had lesions over the face. Thirteen (81.25%) had a large solitary plaque extending over the nose and a large part of the cheeks and three (18.75%) had multiple lesions. Lesions were central/nasal in two (12.5%), unilateral/asymmetrical in four (25%) and bilateral/symmetrical in 10 (62.5%). Morphological patterns included erythematous/infiltrated (7), psoriasiform (6), ulcerated/crusted (2) and Discoid lupus erythematosus (DLE)[G1] like (1)., Conclusion: Lupoid CL is not strictly a chronic form of disease, which presents on the face from the very onset and shows no scarring or recurrence.

Skin manifestations of tuberculous infection (Mycobacterium tuberculosis) are represented by miliary tuberculosis of the skin, tuberculous chancre, scrofuloderma, tuberculosis verrucosa cutis, periorificial tuberculosis, and lupus vulgaris (LV). Among this group, LV is the most common skin condition, diagnosed in 10% of tuberculotic patients. The authors report herein a case of squamous cell carcinoma (SCC) arising from long-standing (50-year) LV and underline the need of an extensive follow-up of tuberculotic lesions.

Background: A 65-year-old man is described with a 40-year history of lupus vulgaris exfoliativus, a form of cutaneous tuberculosis that resembles psoriasis. He had been misdiagnosed as having psoriasis vulgaris for many years. A cutaneous squamous cell carcinoma developed within a plaque of lupus vulgaris exfoliativus., Methods: A skin biopsy provided the correct diagnoses., Results: The patient was successfully treated with medication for tuberculosis and had his skin cancer cured by surgical excision., Conclusions: With an increasing worldwide incidence of tuberculosis, one needs to be aware of its cutaneous forms and variants, as well as its complications, in particular skin cancer. Lupus vulgaris exfoliativus may resemble psoriasis vulgaris.

A 14-year-old girl presented with a 10-year history of a large crusted plaque over the right thigh for 10 years and small reddish plaque over the left upper back for 3 months. On routine evaluation, she was found to have hematuria. Skin biopsy from the lesion was suggestive of skin tuberculosis (lupus vulgaris), and kidney biopsy showed features of IgA nephropathy (IgAN). Fine-needle aspiration from the inguinal lymph node was consistent with granulomatous disease. The patient has been on anti-tubercular treatment, and the hematuria has subsided.

Lupus vulgaris (LV) is the most frequent cutaneous tuberculosis, representing more than 55% of the tuberculoses with this location. Malignization can occur after a long latency (10-30 years), in 1-2% of the cases, and it is mainly in squamous cell carcinoma. The histological exam is highly important in the observation of neoplasic transformations. The authors present a 59-years-old female patient, from the rural environment, working as a farmer, with lupus vulgaris developing since her first childhood years. It started at the age of 2 years, at the right ear lobule, after the empiric perforation for earrings. The evolution was progressive, eccentric, interesting the pinna and the right cheek in the meanwhile. At the first examination, in 2002, a diffuse mass of red-yellowish infiltration was found at the level of the right ear and the right cheek. In the following two years, an ulcero-vegetating tumor developed at the level of the right ear lobule, accompanied by the presence of a right retromandibular adenopathy, of about 1 cm, which was proved by the histopathologic exam to be a squamous cell carcinoma developed from a lupus vulgaris. After scraping out the right retromandibular ganglion, detected by palpation, a histological exam showed ganglion metastasis.

Tuberculosis is still a significant problem in developing countries. Cutaneous forms of tuberculosis account for approximately 10% of all cases of extrapulmonary tuberculosis. Cutaneous tuberculosis may be because of true infection with Mycobacterium tuberculosis or because of tuberculids. Tuberculids are immunological reactions to haematogenously spread antigenic components of M. tuberculosis. True cutaneous tuberculosis may be because of inoculation or haematogenous spread of M. tuberculosis to the skin. Lupus vulgaris is the commonest form of true cutaneous tuberculosis. Other forms of true cutaneous tuberculosis are tuberculous chancre, tuberculosis verrucosa cutis, scrofuloderma, periorificial tuberculosis and miliary tuberculosis of the skin. Lupus vulgaris is usually chronic and progressive. It occurs in patients with moderate to high immunity against M. tuberculosis as evidenced by strongly positive tuberculin test. Long-standing cases of lupus vulgaris may be complicated by squamous cell carcinoma (SCC). We describe a patient who had undiagnosed lupus vulgaris for 35 years until she developed SCC on the lesion of lupus vulgaris.

Introduction: Pulmonary hypertension (PH) is a serious complication of lupus. The effectiveness of current vasoactive therapy has not been well described., Methods: Retrospective analysis of 12 patients with lupus-associated PH (age 43+/-10 years, mean+/-SD, all female) treated with pulmonary vasodilators., Results: At baseline, patients had severe PH: median six-minute walk distance (6MWD) 266 m (95% confidence interval [CI], 106 to 362); functional class III (n=7) and IV (n=5); mean pulmonary artery pressure (mPAP) 52 mmHg and cardiac index 2.23 L/min/m(2). Eight patients were started on epoprostenol and 2 each on bosentan or treprostinil. After a mean follow-up of 41+/-25 months, 5 patients were on combination therapy (3 epoprostenol plus bosentan, 1 treprostinil plus bosentan, 1 bosentan plus sildenafil) and 7 were on monotherapy (2 epoprostenol, 4 bosentan, 1 sildenafil); 6MWD increased by 139 m (95% CI, 36 to 259, p=0.007), 8 patients were functional class I or II and 4 were class III; right ventricular systolic pressure (RVSP) decreased by 22 mmHg (95% CI, 6 to 36; p=0.012), mPAP decreased by 18 mmHg (95% CI, 8 to 29; p=0.014), and cardiac index increased by 1.44 L/min/m(2) (95% CI, 0.76 to 2.08; p=0.016). There was no mortality or need for lung transplantation. Therapy was well tolerated., Conclusions: Vasoactive therapy can achieve sustained clinical and hemodynamic improvement in lupus-associated PH.

Background: Matrix metalloproteinases (MMPs) have been implicated to play important roles in a number of pathological processes such as inflammation. In human glomeruli, the mesangial matrix turnover is controlled by a dynamic equilibrium between synthesis and degradation to which metalloproteinases are known to contribute. Metalloproteinase-11 (MMP-11) was originally discovered as a gene whose expression was associated with tissue remodelling. The aim of this study was to investigate whether MMP-11 protein is expressed in various types of glomerulonephritis and to elucidate the role of this expression., Methods: Using standard immunohistochemistry, we analysed MMP-11 expression in renal biopsies from 95 patients with primary glomerulonephritis (n = 44) and secondary, either lupus-associated glomerulonephritis (n = 22) or pauci-immune, ANCA-associated glomerulonephritis due to small vessel vasculitis (n = 23) or Wegener's granulomatosis (n = 6). The examined cases were divided into two groups (proliferative and non-proliferative). Anti-Ki67 and -CD68 immunostaining was also performed in order to estimate cell proliferation and number of macrophages, respectively., Results: MMP-11 immunopositivity was detected in the glomeruli of the majority of pathological samples. The highest incidence of MMP-11 immunopositivity (26.3%) was noticed in glomerulonephritides associated with microscopic polyangiitis and Wegener's granulomatosis. Generally, MMP-11 was often expressed in segmental areas of sclerosis, microadhesions, cellular and fibrocellular crescents. Fibrotic crescents and fibrotic glomeruli were constantly MMP-11-immunonegative. In MMP-11 immunoreactive glomeruli, increased numbers of macrophages were often detected in the mesangium (P = 0.001), while no such observation could be made with regard to proliferating cells (P = 0.170)., Conclusions: MMP-11, like an inflammatory mediator, may exert a chemotactic influence on macrophages which aggregate in the mesangium; MMP-11 is not likely to have a parallel mitogenic or antifibrotic effect in diseased glomeruli.

Although systemic lupus erythematosus (SLE) is usually evaluated with regard to autoimmune reactivity toward the kidney, there are multiple psychiatric abnormalities associated with this autoimmune disease. Lupus-prone male NZM88 mice, derived from NZB/NZW F1 mice, develop early neuropsychiatric manifestations without any signs of nephritis. In addition to the usual repertoire of antibody specificities, including autoantibodies to dsDNA and renal antigens, mice of this inbred strain express autoantibodies to numerous brain antigens. Here, we show that autoantibodies to brain antigens, assessed by Western analysis, are as individually varied as are the diverse neuropsychiatric manifestations observed in SLE patients. Additionally, a monoclonal antibody derived from the spleen of an untreated NZM88 male when injected into healthy BALB/cByJ, but not C57BL/6J, mice induced behaviors similar to those of lupus-prone NZM88 mice. This monoclonal antibody, which is specific to dynamin-1, binds preferentially in BALB/cByJ cortex and induces substantial expression of cytokines mainly in the hypothalamus. Thus, an antibody to just one brain antigen can induce multiple behavioral changes, and multiple autoantibodies to different brain antigens exist in lupus-prone mice; however, susceptibility to the induction of neurobehavioral deficits is dependent on host genetics.

Torque teno virus (TTV), currently classified into the family Circoviridae, genus Anellovirus, was first found in a patient with non-A-E hepatitis. TTV has a single stranded circular DNA of approximately 3.8 kb. TTVs are extraordinarily diverse, spanning five groups including SANBAN and SEN viruses. Torque teno mini virus (TTMV) with approximately 2.9 kb genome also has wide variants. Recently, two related 2.2- and 2.6-kb species joined this community. Recombinations between variants are frequent. This extensive TTV diversity remains unexplained; it is unclear how TTVs could be viable, and why they require such genetic variation. An unequivocal culture system is still not available. TTVs are ubiquitous in > 90% of adults worldwide but no human pathogenicity of TTV has been fully established. Epidemiological surveys need to specify the variants being studied and clinical targets, and must calibrate the sensitivity of the assay used. Potentially interesting observations include a higher viral load in patients with severe idiopathic inflammatory myopathies, cancer and lupus. Active replication was also found in infants with acute respiratory diseases. TTV/TTMV-related viruses were found in chimpanzees, apes, African monkeys and tupaias, and also in chickens, pigs, cows, sheep and dogs. Experimentally, rhesus monkeys were persistently infected by TTV, but only 1/53 chimpanzees. TTV transcribes three species of mRNAs, 3.0-, 1.2- and 1.0-kb in the ratio of 60:5:35. Recently, at least three mRNAs were shown in chicken anaemia virus. The genomic region -154/-76 contains a critical promoter. TTV seems to have at least three proteins; however, the definite functions of these proteins await further research work., (Copyright 2006 John Wiley & Sons, Ltd.)

An otherwise healthy 5-week-old infant with erythematous plaques predominantly on the face and scalp presented to our dermatology clinic. The mother had been diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent. Neonatal lupus is a rare condition associated with transplacental transfer of IgG anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus. Active connective tissue disease in the mother does not have to be present and in fact is often absent. Although the cutaneous, hematologic and hepatic manifestations are transient, the potential for permanent heart block makes it necessary for this to be carefully ruled out. As in this case, the dermatologist may be the one to make the diagnosis and should be aware of the clinical presentation, work-up, and management of this important disease.

Introduction: Acute adrenal insufficiency during antiphospholipid syndrome is usually due to a bilateral adrenal hemorrhage. For a patient, an unilateral involvement has induced an acute adrenal insufficiency., Case Report: A patient with an antiphospholipid syndrome has developed an acute adrenal insufficiency with an unilateral adrenal hemorrhage. This complication was caused by a concurrent steroid therapy, for an associated lupus, which resulted in a suppression of the contralateral adrenal gland., Conclusion: In patients with antiphospholipid syndrome and concurrent steroid therapy, usually for lupus, unilateral adrenal hemorrhage can cause acute adrenal insufficiency. Withdrawal of steroid might be difficult in case of undetected bilateral hemorrhage.

Background and Purpose: Systemic lupus erythematosus (SLE), a prototype of systemic autoimmune disease characterized by multiorgan involvement with diverse clinical and serological manifestations, principally affects women in their child-bearing years. Clinically significant hepatic abnormality as the initial presentation of SLE has rarely been reported., Methods: Eleven patients with lupus with initial presentation of lupus-related hepatitis were included in this retrospective review. Clinical manifestation, immunological profiles, and risk factors for poor prognosis were analyzed., Results: The most commonly associated clinical manifestations were found to be thrombocytopenia, leukopenia, advancing age, and presence of anti-SSA/Ro antibody and anti-thyroid antibodies. The diagnosis of SLE was delayed due to dominant hepatic abnormalities. Age greater than 50 years and marked hepatic decompensation in accordance with Child classification B and C might suggest poor prognosis (p=0.06). However, the p value was not statistically significant because of the small sample size., Conclusions: Lupus-related hepatitis, particularly in late-onset lupus, is common. In addition, the presence of anti-SSA, anti-thyroglobulin, and anti-microsomal antibodies is indicative of hepatic involvement in patients with SLE.

Cardiac involvement is one of the main complications substantially contributing to the morbidity and mortality of patients suffering from systemic autoimmune diseases. All the anatomical heart structures can be affected, and multiple pathogenic mechanisms have been reported. Non-organ-specific autoantibodies have been implicated in immune complex formation and deposition as the initial triggers for inflammatory processes responsible for Libman-Sacks verrucous endocarditis, myocarditis and pericarditis. Anti-phospholipid antibodies have been associated with thrombotic events in coronary arteries, heart valve involvement and intra-myocardial vasculopathy in the context of primary and secondary anti-phospholipid syndrome. Antibodies-SSA/Ro and anti-SSB/La antigens play a major pathogenic role in affecting the heart conduction tissue leading to the electrocardiographic abnormalities of the neonatal lupus syndrome and have been closely associated with endocardial fibroelastosis.

Inducible costimulator (ICOS) is a costimulatory molecule expressed in activated T cells and plays an important role in T-cell-dependent immune responses. We investigated the role of ICOS in the development of autoimmune diseases in MRL/Mpj-lpr/lpr (MRL/lpr) mice. ICOS was expressed on CD4(+) T cells from adult MRL/lpr mice. ICOS-deficient MRL/lpr mice showed mild lymphoadenopathy and a decreased memory type CD4(+) T cells in the spleen. The anti-dsDNA antibody levels were decreased. CD4(+) T cells from ICOS-deficient MRL/lpr mice showed less of a bias to Th1 and an enhanced production of IL-4 in response to anti-CD3 antibody in comparison to those from wild-type MRL/lpr mice. Although ICOS-deficiency abrogated renal vasculitis completely, the severity of glomerulonephritis was not altered. ICOS is considered to play a role in CD4(+) T cell activation, autoantibody production, and renal vasculitis. However, it is not essentially required in the development of glomerulonephritis.

Lupus vulgaris and scrofuloderma are the opposite poles of cutaneous tuberculosis. Lupus vulgaris of a giant size and scrofuloderma in the vicinity of this lesion were both present in a 70-year-old female patient. The purified protein derivative of tuberculin (PPD) skin test was strongly positive. In histopathological examination, granulomatous infiltration without caseation necrosis was seen in the dermis. The patient was treated with a four-drug therapy consisting of pyrazinamide (25 mg/kg), isoniazid (5 mg/kg), rifampin (10 mg/kg) and ethambutol (15 mg/kg) daily for 2 months, followed by dual therapy with isoniazid and rifampin for 6 months. Her cutaneous lesions significantly regressed after 4 months, leaving keloid scars.

Medio-facial mutilations are a real problem from a diagnosis and prognosis point of view. Various etiologies may be in question, namely bacterial, parasitic, mycotic, viral infections or yet predisposing factors such as denutrition or a immunodepression. Among these etiologies, the lupus tuberculosis remains a major concern to be taken into account in poor socio-economic background. We report two cases of lupus tuberculosis in teen-agers whose diagnosis difficulty induced sequellae although limited by a further appropriate care management. The clinical spectrum of the cutaneous tuberculosis and the place of this affection featuring ahead of other medio-facial mutilations etiologies remain important in tropical area.

Cutaneous tuberculosis may be associated with concurrent systemic foci in the body such as lung, lymph node, bone or CNS. Phlyctenular keratoconjunctivitis (PKC) is a manifestation of immunological response to a variety of antigens in the eye, tubercular focus (evident or occult) being the commonest in India. Reports in the existing literature have shown lungs and lymph nodes to be the predominant underlying focus associated with PKC, whereas cutaneous tuberculosis has seldom been found in this situation. We report this forgotten association in two children with cutaneous tuberculosis, one each with lupus vulgaris and scrofuloderma, who also had PKC. Interestingly, one of the cases also had simultaneous lichen scrofulosorum, which is also an immunological response to tubercular antigen and manifests in the skin, thus showing immunological manifestation in two different organ systems along with cutaneous focus of tuberculosis.