Monogenic autoimmune diseases (AD) present as lupus-like clinical manifestations with recurrent fever or various vasculopathies. Recurrent fever with an elevation of acute phase reactants and various skin lesions are similar in monogenic AD and autoinflammatory disease. The molecular pathogenesis of adult systemic erythematosus can be understood through monogenic AD based on gene defects: complement, apoptosis, interferonopathy via nucleic acid sensing, tolerance, rasopathies, and others. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common occurrences in type I interferonopathy. Some syndromes have been reported to present with autoimmune inflammation and the general clinical findings, including cerebral calcification. Various clinical manifestations in monogenic AD present in accordance with the gene loss- or gain-of-function mutations involved. The monogenic AD for the early onset of more severe lupus-like symptoms or vasculopathy needs to be considered. Furthermore, clinical trials were conducted via targeted therapy for related molecular pathways, because conventional treatments were not effective in managing monogenic AD.
Acute-Phase Proteins ; Adult ; Apoptosis ; Autoimmune Diseases* ; Chilblains ; Complement System Proteins ; Fever ; Humans ; Inflammation ; Interferons ; Livedo Reticularis ; Lung Diseases, Interstitial ; Lupus Erythematosus, Systemic ; Panniculitis ; Skin

Rheumatoid vasculitis is a rare, but most serious extra-articular complications of long-standing, seropositive rheumatoid arthritis (RA). Vasculitis of hepatic artery is an extremely rare but severe manifestation of rheumatoid vasculitis. A 72-year-old woman who presented with polyarthralgia for 2 months was diagnosed with early RA. Since she had manifestations of livedo reticularis, and liver dysfunction which was atypical for RA patients, a percutaneous needle liver biopsy was performed revealing arteritis of a medium-sized hepatic artery. Extensive investigations did not reveal evidences of other systemic causes such as malignancy or systemic vasculitis. The patient was diagnosed with rheumatoid vasculitis involving hepatic arteries based on Bacon and Scott criteria for rheumatoid vasculitis. With high dose corticosteroid and cyclophosphamide induction and methotrexate and tacrolimus maintenance treatment, she was successfully recovered. Association of rheumatoid vasculitis at very early stages of the disease may represent an early aggressive form of RA.
Aged ; Arteritis ; Arthralgia ; Arthritis, Rheumatoid* ; Biopsy ; Cyclophosphamide ; Female ; Hepatic Artery* ; Humans ; Livedo Reticularis ; Liver ; Liver Diseases ; Methotrexate ; Needles ; Rheumatoid Vasculitis* ; Systemic Vasculitis ; Tacrolimus ; Vasculitis

BACKGROUND AND PURPOSE: Postural tachycardia syndrome (POTS) is a syndrome of orthostatic intolerance in the setting of excessive tachycardia with orthostatic challenge, and these symptoms are relieved when recumbent. Apart from symptoms of orthostatic intolerance, there are many other comorbid conditions such as chronic headache, fibromyalgia, gastrointestinal disorders, and sleep disturbances. Dermatological manifestations of POTS are also common and range widely from livedo reticularis to Raynaud's phenomenon. METHODS: Questionnaires were distributed to 26 patients with POTS who presented to the neurology clinic. They were asked to report on various characteristics of dermatological symptoms, with their answers recorded on a Likert rating scale. Symptoms were considered positive if patients answered with "strongly agree" or "agree", and negative if they answered with "neutral", "strongly disagree", or "disagree". RESULTS: The most commonly reported symptom was rash (77%). Raynaud's phenomenon was reported by over half of the patients, and about a quarter of patients reported livedo reticularis. The rash was most commonly found on the arms, legs, and trunk. Some patients reported that the rash could spread, and was likely to be pruritic or painful. Very few reported worsening of symptoms on standing. CONCLUSIONS: The results suggest that dermatological manifestations in POTS vary but are highly prevalent, and are therefore of important diagnostic and therapeutic significance for physicians and patients alike to gain a better understanding thereof. Further research exploring the underlying pathophysiology, incidence, and treatment strategies is necessary.
Arm ; Exanthema ; Fibromyalgia ; Headache Disorders ; Humans ; Incidence ; Leg ; Livedo Reticularis ; Neurology ; Orthostatic Intolerance ; Postural Orthostatic Tachycardia Syndrome* ; Primary Dysautonomias ; Tachycardia ; Varicose Veins

Livedo racemosa (LR) is characterized by a striking violaceous netlike patterning of the skin similar to the livedo reticularis, from which it differs by its localization (more generalized), and shape (irregular, broken circular segments). LR is probably caused by patchy impairment of cutaneous arteriolar circulation, resulting in venous dilatation and stasis of blood. LR is always associated with a pathological condition, including hematologic/hypercoagulable disease, vasculitis, connective tissue diseases, neoplasm, lymphoma, infection, cerebrovascular disease, adverse response to a drug, and etc. Hence, clinical, pathological and laboratory examinations are important for excluding these underlying diseases. To date, there have been few reports of LR secondary to posttransplant lymphoproliferative disease (PTLD) in dermatologic literatures. Herein, we report a case of LR associated with Epstein-Barr virus-induced PTLD of cervical lymph node in a 19-year-old female, who had generalized reticular erythematous to violaceous patch on the entire body after allogenic peripheral blood stem cell transplantation.
Connective Tissue Diseases ; Dilatation ; Female ; Herpesvirus 4, Human ; Humans ; Livedo Reticularis ; Lymph Nodes ; Lymphoma ; Lymphoproliferative Disorders ; Peripheral Blood Stem Cell Transplantation ; Skin ; Strikes, Employee ; Vasculitis

We report a 62-year-old woman with multiple myeloma associated with cryoglobulinemia accompanied by gangrene of the digits. She presented with generalized purplish net-like discoloration (livedo reticularis), which was more prominent in the lower extremities. Multiple small shallow ulcers with crusts were found in places. In addition, gangrene was observed in both ear helices, both index fingers, and several toes. The patient had monoclonal gammopathy consisting of IgG and kappa (3.95 g/dL), cryoglobulinemia, and bone marrow plasmacytosis (42%). A biopsy of a discolored skin patch on the lower leg revealed leukocytoclastic vasculitis. She was diagnosed with multiple myeloma associated with cryoglobulinemia. Immediate plasmapheresis halted the progression of the skin lesions and digital gangrene. Two cycles of thalidomide plus dexamethasone therapy led to a partial response. This case highlights the need to search for cryoglobulinemia and multiple myeloma when we see livedo reticularis or multiple skin ulcers with obscure causes.
Biopsy ; Bone Marrow ; Cryoglobulinemia ; Dexamethasone ; Ear ; Female ; Fingers ; Gangrene ; Humans ; Immunoglobulin G ; Leg ; Livedo Reticularis ; Lower Extremity ; Middle Aged ; Multiple Myeloma* ; Paraproteinemias ; Plasmapheresis ; Skin ; Skin Ulcer ; Thalidomide ; Toes ; Ulcer ; Vasculitis*

Livedoid vasculopathy is a rare chronic relapsing disorder characterised by recurrent painful thrombotic and vasculitic ulcers on the legs. We present the cases of two Indian women with livedoid vasculopathy that were found to be associated with an underlying factor V Leiden heterozygous mutation. There were no other thrombotic manifestations, and livedoid vasculopathy was the sole presenting feature of the factor V Leiden mutation, although this could also be coincidental. Initial treatment with high-dose immunosuppressive therapy was suboptimal, and the addition of pentoxifylline and antiplatelet therapy was crucial in achieving disease control and remission. These cases highlight the possible association with an underlying prothrombotic disorder, such as factor V Leiden mutation, in patients with livedoid vasculopathy. Although this association is relatively uncommon, it is more relevant to Indian patients, as the presence of factor V Leiden mutation is highest in this ethnicity as compared to the local Malay and Chinese populations.
Adult ; Blood Vessels ; pathology ; DNA ; genetics ; Factor V ; genetics ; metabolism ; Female ; Humans ; Leg Ulcer ; blood ; genetics ; pathology ; Livedo Reticularis ; blood ; diagnosis ; genetics ; Point Mutation ; Polymerase Chain Reaction ; Skin ; blood supply ; Skin Diseases, Vascular ; blood ; genetics ; pathology

Essential thrombocythemia (ET) is a clonal stem cell disease characterized by isolated thrombocytosis and thrombohemorrhagic complications. We describe an unusual case of ET primarly presenting with skin symptoms including erythromelalgia and livedo reticularis (racemosa-type). Persistent thrombocytosis, bone marrow findings, JAK2 gene mutation, and markedly decreased ristocetin-cofactor activity were consistent with the diagnosis of ET and acquired von Willebrand disease. Elevated antiphospholipid antibodies were also found. The present case highlights the complex nature and diagnostic challenge of myeloproliferative disorders such as ET, which can involve multiple organ systems and often shows a variety of microvascular complications, coagulation anomalies, and autoimmune phenomena.
Antibodies ; Antibodies, Antiphospholipid ; Bone Marrow ; Erythromelalgia ; Humans ; Livedo Reticularis ; Myeloproliferative Disorders ; Skin ; Stem Cells ; Thrombocythemia, Essential ; Thrombocytosis ; von Willebrand Diseases

INTRODUCTIONThis study aims to analyse the clinico-epidemiological characteristics of Asian patients diagnosed with livedo vasculopathy (LV).

MATERIALS AND METHODSWe performed a retrospective analysis of all patients diagnosed with LV from 1997 to 2007 at our centre.

RESULTSSeventy patients were diagnosed with LV with a mean age of 39 years, female: male ratio of 3:1 and no racial predilection. Most cases remained purely cutaneous, presenting with painful leg ulcers and atrophie blanche. Peripheral neuropathy was the only extra-cutaneous complication (9%). In patients who were screened, associations included hepatitis B (7%) and hepatitis C (4%), positive anti-nuclear antibody (14%), positive anti-myeloperoxidase antibody (5%), positive anti-cardiolipin antibodies (7%) and positive lupus anticoagulant (2%). In 49 patients who achieved remission, 55% required combination therapy, most commonly with colchicine, pentoxifylline and prednisolone. In those treated successfully with monotherapy, colchicine was effective in 59% followed by prednisolone (17.5%), pentoxifylline (17.5%) and aspirin (6%). Mean follow-up period was 50 months.

CONCLUSIONLV in Asian patients is a high morbidity, chronic relapsing ulcerative skin condition. Most patients require induction combination therapy for remission. As further evidence emerges to support a procoagulant pathogenesis, a standardised protocol is needed to investigate for prothrombotic disorders during diagnosis.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Cellulitis ; complications ; epidemiology ; pathology ; Female ; Humans ; Livedo Reticularis ; complications ; epidemiology ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Singapore ; epidemiology ; Skin ; pathology ; Time Factors ; Young Adult

PURPOSE: Blue toe syndrome consists of blue or purplish toes in the absence of a history of obvious trauma, serious cold exposure, or disorders producing generalized cyanosis. It is a life-threatening and still underrecognized disease. It can be commonly occurred by vascular surgery, invasive cutaneous procedures or anticoagulant therapy. Our case is presented of blue toe syndrome related to atheromatous embolization that was presumably triggered by angio CT. METHODS: A 69-year-old man presented with the suddenly developed pain, cyanosis and livedo reticularis of the toes in right foot. Dorsalis pedis pulses were palpable. He had been performed a diagnostic angio CT 1 month earlier. Angio CT revealed diffuse aortic atheromatous plaque in lower abdominal aorta and both common iliac artery. One month after angio CT, he visited our clinic. There was no visible distal first dorsal metatarsal artery and digital artery of right first toe in lower extremity arteriography. A diagnosis was established of blue toe syndrome. Because his symptom was aggravated, we performed the exploration of the right foot. After exposure of first dorsal metatarsal artery, microsurgical atheroembolectomy was done. RESULTS: There were no postoperative complications. After three months the patient had no clinically demonstrable problems. CONCLUSION: Patient with blue toe syndrome is at high risk of limb loss and mortality despite treatment. Blue toe syndrome produces painful, cyanosed toes with preserved pedal pulses. It needs to be aware of blue toe syndrome. Careful history should reveal the diagnosis. Treatment is controversial, however, most believe that anticoagulation therapy should be avoided.
Aged ; Angiography ; Aorta, Abdominal ; Arteries ; Blue Toe Syndrome ; Cold Temperature ; Cyanosis ; Extremities ; Foot ; Humans ; Iliac Artery ; Livedo Reticularis ; Lower Extremity ; Metatarsal Bones ; Postoperative Complications ; Toes

A 65-year-old woman was admitted due to poor oral intake and a dry cough over the previous 3 months. The physical examination was remarkable for bibasilar crackles, and plain chest radiography showed reticulation in both lower lung fields. A pulmonary function test demonstrated a restrictive pattern with a reduced diffusing capacity of the lung for carbon monoxide. High resolution computed tomography showed reticulation and honey-combing in both peripheral lung zones, which was consistent with usual interstitial pneumonia pattern. Her skin showed livedo reticularis. The erythrocyte sedimentation rate and C-reactive protein level were elevated, and hematuria was noted on urinary analysis. A serologic test for auto-antibodies showed seropositivity for Myeloperoxidase-Anti-neutrophil cytoplasmic antibody (MPO-ANCA). A kidney biopsy was performed and showed focal segmental glomerulosclerosis. She was diagnosed as having pulmonary fibrosis with microscopic polyangiitis (MPA) and treated with high dose steroids. Here we report a case of pulmonary fibrosis coexistent with microscopic polyangiitis.
Aged ; Antibodies, Antineutrophil Cytoplasmic ; Biopsy ; Blood Sedimentation ; C-Reactive Protein ; Carbon Monoxide ; Cough ; Cytoplasm ; Female ; Glomerulosclerosis, Focal Segmental ; Hematuria ; Humans ; Idiopathic Pulmonary Fibrosis ; Kidney ; Livedo Reticularis ; Lung ; Microscopic Polyangiitis ; Physical Examination ; Pulmonary Fibrosis ; Respiratory Function Tests ; Respiratory Sounds ; Serologic Tests ; Skin ; Steroids ; Thorax