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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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He subsequently joined the Division of Immunology at Cambridge University (UK) as an EMBO postdoctoral fellow and Marie Curie Fellow from 2000-2003. He did a second post-doctoral stint at the Department of Immunology of Weizmann Institute of Science (2004) in Israel and short stages as visiting scientist at the Center for Neurologic Diseases, Brigham & Women Hospital, Harvard Medical School (2013, 2015). 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Major difference between urticarial vasculitis and urticaria is the duration of lesions. Urticarial lesions regress in 24 hours, but UV lesions persist longer than 24 hours. Residual hyperpigmentation, constitutional symptoms like fever, arthralgia, and abdominal pain are other main clinical differences between these disorders [1]. UV lesions can be pruritic but more commonly these lesions are associated with symptom of burning. Skin biopsy shows histopathologic features of leukocytoclastic vasculitis [2]. Lesions usually persist for several months but very rarely they persist for years [3]. UV may be seen as a manifestation of a systemic disease or it may develop into a systemic illness by itself [2].
\nUV is a rare condition and the exact incidence is not known as a result of small number of literature reports. UV frequency is reported to be between 2 and 20% in chronic urticaria patients and if histologic definition of vasculitis is used as a criterion for diagnosis then the estimate of the prevalence of UV in chronic urticaria patients becomes approximately 5% [1, 3, 4]. Approximately 80% of UV patients have underlying or associated disease [2]. UV is more common in women and very rare in children [4]. Case report of an infant with UV is the only case report presenting the literature [5]. The peak incidence of the disease is in the fourth decade of life [4].
\nUV is a small vessel vasculitis and an immune-complex mediated disease like other leukocytoclastic vasculitis. Leukocytoclastic vasculitis is an example for type III immune reaction, which is characterized with circulatory immune complexes [6]. Initially antigen-antibody complex is formed in blood and then accumulation of the vessel walls. This complex reaction leads to the activation of complement system by the classical pathway. Anaphylatoxins C3a and C5a induce mast cell degranulation and cytokine synthesis. Mast cells release tumor necrosis factor alpha (TNFα), prostaglandins, histamine, heparin, platelet activating factor, leukotrienes, neutrophil chemotactic factor A, neutral protease, and tryptase [6]. Increase in cytokine and chemokine production results in edema and tissue reaction. Main antibodies in this reaction are IgG or IgM, and rarely IgA. The antigen in the complex may be autologous or it may derive from exogenous origin such as an infection or drugs [4]. But the antigens are mostly not known [1]. Based on the level of complement, UV is divided into two subgroups: normocomplementemic UV (NUV) and hypocomplementemic UV (HUV) [7]. UV is often idiopathic, but in some cases, it can be triggered with drugs, infection (hepatitis B and hepatitis C), connective tissue disease, neoplasia, cold, and exercise. [3, 8–12]. Drugs were found to be responsible for 10% of UV patients. The risk of UV is irrespective of both dose and frequency [8]. Infliximab, procainamide, antidepressants, methotrexate, sulfamethoxazole-trimethoprim, diltiazem, cimetidine, enalaprilin, and nonsteroid anti-inflammatory drugs (NSAIDs) are the main drugs reported in the literature [3, 13]. A patient with UV should also be examined for underlying diseases like viral infections, monoclonal gammopathies, serum sickness, and serum sickness like reactions, SLE, Sjögren’s syndrome (SS) or mixed cryoglobulinemia [2, 14, 15]. Polycythaemia rubra vera [16], essential thrombocythemia [17], systemic sclerosis [18], acquired reactive perforating collagenosis [19], lymphoma [20], leukemia [21, 22], and thyroid dysfunction [23] are the other systemic diseases reported in the literature. UV patients with normal serum complement levels have rarely systemic manifestations. By contrast, UV patients with decreased C3 and C4 have systemic diseases including lung, kidney, and eye involvement [14]. At the same time, HUV patients may have extracutaneous symptoms like fever, myalgia, malaise, fatigue, arthralgia, conjunctivitis, episcleritis, nephritis, and cardiac valve involvement [8, 24]. A small group of patients with HUV also have anti-C1q antibodies (anti-C1q Ab), and this group is considered as a separate entity called HUVS [7]. Ig G autoantibodies to the collagen like region of C1q (anti-C1q Ab) were detected in HUVS patients’ serum. Anti-C1q Abs were also detected in patients with systemic lupus erythematosus (SLE) and 85% of these patients had glomerulonephritis. Anti-C1q Ab is associated with glomerulonephritis in SLE patients [2]. However, all HUVS patients have UV lesions and anti-C1q Ab, but only a group of SLE patients have UV lesions [2]. UV occurs in 5–10% of SLE patients and 28–47% of SLE patients have anti-C1q Ab [14]. HUVS patients form a small fraction of idiopathic HUV group (less than 5%), and these patients may have gastrointestinal, neurologic, ophthalmologic, renal, and pulmonary involvement [7]. Pulmonary disease in patients with HUVS was first described in 1982 with an incidence of 50%. However, these patients had history of tobacco exposure. After this report, different incidences (15–50%) were reported in HUVS patients. The exact mechanism of obstructive lung disease is not known but vasculitis of pulmonary capillaries, dysfunction of α 1 antitrypsin and binding of anti-C1q Ab to the surfactant proteins in pulmonary alveoli are the possible hypotheses for pathogenesis [14]. Renal disease was also reported in 20–30% of patients with HUVS [25].
\nUV is characterized by widespread urticarial lesions each lasting longer than 24 hours clinically [12, 26]. Classically urticarial plaques of UV are persistent or long lasting (in 64% of patients more than 24 hours) (Figure 1) and may resolve with purpura (Figure 2) or hyperpigmentation (in up to 35% of patients) in comparison to common urticaria [12]. Lesions may be asymptomatic, are usually pruritic and sometimes painful, tender or burning (in 33% of patients) in comparison to intensely pruritic urticarial lesions (Table 1) [12, 27]. UV presents usually with classical wheals but rarely livedo reticularis or even bullae may develop [12]. Angioedema can sometimes accompany urticarial lesions in up to 42% of UV patients [4, 12]. In a study reported it was detected that angioedema was present in 13% of HUV and 23% of NUV cases [28]. Following angioedema, a residual bruising may develop [12]. Typically clinical lesions of UV are recurrent and persist for more than 4–6 weeks even years [27]. As there are different clinical presentations of UV lesions, a biopsy is crucial in establishing a definite diagnosis [12]. All patients show histopathological evidence of leukocytoclastic vasculitis on biopsy [28].
\nUrticarial lesions on the dorsal trunk of 47 years old male that is present for a month. The histopathological examination revealed lymphocytic vasculitis and laboratory examinations yield a diagnosis of accompanying Sjögren syndrome.
Widespread urticarial lesions with central purpura located on left lateral thigh of 85 years old female patient.
Clinical characteristic | \nUV | \nCommon urticaria |
---|---|---|
Lesion predilection | \nDependent areas, areas under focal pressure, anywhere | \nAnywhere |
Symptoms | \nPainful, tender, burning, pruritic | \nIntensely pruritic |
Persistence | \nMore than 24 hours [usually 24–72 hours] | \nLess than 24 hours [usually 30 minutes–24 hours] |
Residual signs | \nPurpura or hyperpigmentation | \nNone |
Clinical characteristics of cutaneous lesions of UV in comparison with common urticaria.
Upon confirmation of diagnosis, patients are divided into two major categories on the basis of serum complement levels: normocomplementemic UV (NUV) and hypocomplementemic UV [HUV] cases [28]. Many UV patients have NUV [27]. UV patients also frequently present with systemic manifestations (Table 2) [26]. The most commonly observed systemic manifestation of UV is termed as “AHA syndrome”: arthralgias and arthritis, hives and angioedema [12]. Like in the situation of cutaneous lesions, common urticariais still in the differential diagnosis of systemic manifestations of UV as common urticariacan rarely has angioedema and systemic symptoms like arthralgia or abdominal pain [12]. Systemic manifestations of UV develop mostly in hypocomplementemic patients [12]. HUV patients frequently have an underlying systemic disease [26, 29]. Systemic manifestations of HUV patients occur regardless of being idiopathic (primary HUV) or associated with an underlying disease (secondary HUV) [12]. Clinical features of UV can exacerbate with some situations like emotional stress, anxiety, exercise, and excessive alcohol consumption [12]. Additionally, heat and spicy foods can increase the pruritus and/or urticarial lesions [30]. UV lesions can develop under pressure of tight and narrow clothing [30]. Smokers can develop more severe respiratory involvement and progression to COPD in HUV patients [31]. UV can sometimes develop in striae distensae and can present a diagnostic challenge in pregnancy [13]. UV can sometimes be a presenting sign of SLE or present with a clinical picture similar to SLE [12, 28]. Some patients have autoimmune idiopathic HUV with a lupus-like clinical picture, hence termed HUVS [2, 27]. HUVS patients usually have accompanying systemic involvement involving more than one organ system [26]. These patients presenting clinically as HUVS are mostly young women and many aspects of the clinical picture are similar to SLE [12, 28]. Schnitzler syndrome is another clinical condition related to UV [32]. It is defined as the presence of UV in association with mostly IgM monoclonal gammopathy and increased markers of systemic inflammation [32].
\nOccurrence | \nSystemic features |
---|---|
Common | \nMusculoskeletal: arthralgia, arthritis |
Less common | \nRespiratory: cough, dyspnea, hemoptysis, COPD, asthma, pleural effusion Renal disease: hematuria, proteinuria, glomerulonephritis Gastrointestinal: substernal pain, abdominal pain, nausea, vomiting, diarrhea |
Rare | \nCardiac: pericarditis, pericardial effusion, cardiac tamponade Ophthalmologic: conjunctivitis, episcleritis, uveitis, geographic serpiginous choroidopathy, visual loss Other: fever, splenomegaly, lymphadenopathy, cold sensitivity, reversible tracheal stenosis |
Very rare | \nCNS: pseudotumor cerebri, cranial nerve palsies, aseptic meningitis Miscellaneous: transvers myelitis, cardiac valve disease, optic atrophy, Jaccaud’s syndrome [chronic postrheumatic fever arthropathy], peripheral neuropathy, pleuritis |
Clinical features of systemic involvement in UV.
Patients can present with general constitutional symptoms, like fever, arthralgias, malaise, and fatigue [12]. Most UV patients have musculoskeletal involvement presenting as arthralgia or arthritis [12, 26, 28]. Jaccoud’s syndrome or arthropathy was defined as joint deformities similar to that of rheumatoid arthritis [12]. It consists of ulnar deviation of the fingers, swan neck deformities and subluxations in the hands [12]. This hand deformity is most commonly associated with SLE and rarely with HUV [12]. Ophthalmologic involvement is rare (10% of UV patients) and can present as conjunctivitis, episcleritis, uveitis, or geographic serpiginous choroidopathy leading to visual loss [12]. Eye involvement in the form of episcleritis and uveitis can develop mostly in HUV patients (21%) [28]. Pulmonary involvement may present clinically as cough, dyspnea, hemoptysis, COPD, asthma, pleuritic, emphysema, or pleural effusion [12]. HUVS patients presenting with COPD are usually young smokers, and the observed COPD is more severe than that seen in heavy smoker patients without HUVS [12]. Emphysema can develop in UV patients as a result of leukocytoclastic vasculitis of pulmonary vessels. Lung involvement may present clinically late in the disease process but is a leading cause of morbidity and mortality [12]. Renal disease can occur in 5–10% of patients with HUVS and is discovered by finding proteinuria and microscopic hematuria [12]. Renal involvement can present as glomerulonephritis in 20–30% of HUV cases [12]. Gastrointestinal involvement can present clinically as nausea, vomiting, substernal pain, abdominal pain, diarrhea, or general feeling of gastrointestinal distress [12]. Cardiac involvement can develop rarely [12]. Recurrent pericarditis, pericardial effusion, cardiac tamponade, and cardiac valvular disease have been reported [12]. Several HUVS patients with Jaccoud’s arthropathy were reported to develop valvular heart disease requiring valvular replacement [12, 24, 33, 34]. Central and peripheral nervous systems can rarely be affected [12].
\nConsensus meeting in 1996 stated that long lasting (at least 24 hour–5 days) indurated wheals, which may be itchy, painful, or tender, be associated with purpura and presence of associated extracutaneous findings, and cutaneous vasculitis confirmed by histopathological examination are defined as UV [35]. UV should be suspected in any patient with urticarial lesions lasting more than 24 hours. The prevalence of UV among all patients that present with urticarial lesions is 11% and among patients with chronic urticaria it is 15–20% [23, 36, 37]. To ascertain the exact duration of urticarial lesions, a particular lesion could be encircled with a marking pen and the patient is re-examined 24 hour later to confirm the persistence of urticarial lesions [23]. Diascopy and dermatoscopy can help to suspect UV [23, 38]. The lesions of UV may be non- or partially-blanchable on diascopic examination [23, 38]. It was termed as “disappearing halo test” in which upon diascopy clinically invisible purpura becomes evident as dark red or slightly brown macule in the center of a blanched UV lesion [38]. UV can disclose purpuric dots or globules in a patchy orange-brown background dermatoscopically corresponding to extravasation and degradation of red blood cells due to leukocytoclastic vasculitis [39–41]. These purpuric dots are reddish initially and later they become more purplish [40]. Conversely, urticarial lesions disclose prominent and sometimes reticular red lines corresponding to ectatic and horizontal subpapillary vessels [39–41]. Definitive diagnosis of UV requires a lesion biopsy demonstrating typical histopathological features in addition to the previously described clinical characteristics in a patient presenting with urticarial lesions [4]. Two lesion biopsies, one for routine histopathology and one for direct immunofluorescence, should be obtained [2]. Biopsies should be taken from the early lesions, which are maximum 24–48 hours old [42]. Multiple biopsies may be required to establish a biopsy [42]. In the case, an UV diagnosis is made, the physician should additionally search for the presence of any underlying infectious etiology [43, 44]. The major finding to be searched for is the presence or absence of hypocomplementemia [2]. It was previously reported that 53–82% of UV patients have normal complement levels and hence NUV, 18–47% of UV patients have decreased complement levels and hence HUV [28, 45]. Approximately, 65% of HUV and 45% of NUV patients have systemic involvement [23]. Hypocomplementemic patients are rare (10–20% of all UV patients) and more likely to have systemic involvement and hence they should be appropriately investigated [23, 28, 42, 46]. Optimal classification of UV patients should be done by multiple (two to three) measurements of C1q, C3, C4, and CH50 during clinical observation of several months duration [2]. Measurements should be done during active and quiescent periods [2]. Rare patients with HUVS may have cardiac valvular incompetence with/without Jaccoud’s arthropathy [24, 33, 35, 47]. In 1973, criteria to diagnose HUVS have been proposed [48]. A patient is diagnosed to have HUVS if he/she has two major and at least two minor criteria (Table 3) [48].
\n\n
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\n
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Proposed criteria for diagnosing HUVS.
A patient diagnosed to have UV should be appropriately tested [2]. Complete blood count, ESR, renal and liver functions, urinalysis, ANA, complements, should be examined in all cases with appropriate clinical findings of UV [2]. A scheme would be helpful for planning the laboratory examinations in all patients with clinical UV presentation and specialized tests should be performed in some patients who have clinical clues of systemic involvement [30]. Once basic diagnostic evaluation has been performed, additional laboratory examinations should not be so extensive and should be directed with regard to clues in the history and physical examination [30]. Hematologic examinations can reveal anemia and leukocytosis in nearly half of the patients [49]. Patients with positive anti-C1q antibodies have been detected to have more frequent HUVS, angioedema, livedo reticularis, musculoskeletal, ocular and kidney involvement, and less frequent gastrointestinal and pulmonary involvement than patients without anti-C1q antibodies [46]. These anti-C1q autoantibodies may sometimes be detected in patients having SLE, Good-pasture syndrome or idiopathic membranoproliferative glomerulonephritis without showing signs of urticarial vasculitis [4, 50, 51]. A case having circulating immune complexes and a positive autologous serum skin test was also reported [52]. There are numerous reported cases who were associated with gammopaties and so patients should be appropriately evaluated [53–56]. Soluble serum vascular endothelial-cadherin is detected in systemic vasculitis cases in the acute period, and this can be used as a marker for endothelial cell damage and inflammatory response, but this is nonspecific for UV [57].
\nA lesional biopsy demonstrating the features of UV is the gold standard for diagnosis [4]. The key histopathologic feature is leukocytoclastic vasculitis affecting dermal capillaries and postcapillary venules (Figure 3) [2, 4]. Inflammation is located within the vessel walls and perivascularly [4]. Cellular infiltrate is primarily composed of neutrophils, rarely eosinophils, and lymphocytes may take place (Figure 4) [4]. Lymphocytes predominate in lesions older than 48 hours [23]. In a study, 86% of specimens showed lymphocytic vasculitis, probably due to the age of the lesion biopsied [58]. If these histopathological changes described for UV involve the capillaries and postcapillary venules of the deep dermal layers, subcutaneous tissue, and submucosal connective tissue layers then it is termed as angioedema [2]. Direct immunofluorescence examination shows deposition of immunoglobulins, complement, and/or fibrinogen within and around vessel walls in 58–79% of cases [1, 4, 30, 46]. Basement membrane positive immunofluorescence examination is more frequent in HUV (70–96%) patients than in NUV (1–18%) patients [1]. However, the presence of basement membrane staining in a hypocomplementemic patient may suggest the diagnosis of SLE [30].
\nSuperficial perivascular infiltration and leukocytoclastic vasculitis [Hemotoxylin & Eosin, original magnification ×100] [Courtesy, Onat Akin, MD].
Small vessel vasculitis with neutrophilic infiltration and leukocytoclasia [Hemotoxylin & Eosin, original magnification ×400] [Courtesy, Onat Akin, MD].
The main differential diagnosis of UV is common urticaria [42]. The lesions in urticaria typically resolves in minutes to hours, migrates continually, and leaves no residual pigmentation after resolving in contrast to UV [42]. The main symptom in urticaria is the presence of intense pruritus, UV lesions may present with a more burning sensation [2]. Indurated urticarial lesions of UV are indistinguishable especially from that of chronic spontaneous urticaria [4]. Urticaria lesions may be huge and are usually larger than those of UV [2]. Chronic urticarial lesions are clinically more indurated than that of acute urticaria [4]. Eleven percent of all patients presenting with urticarial lesions are found to have UV [23]. In cases of chronic and antihistamine unresponsive chronic urticaria, when biopsies of lesions were performed, 15–20% of patients were found to have histopathological features of UV and hence diagnosed as UV [36, 37]. So performing a biopsy is necessary to differentiate exactly these two conditions. When patients with acute urticaria are biopsied, histopathology shows sparse cellular infiltrate and moderate to intense dermal edema [4]. Lesions of UV are usually smaller than ordinary urticaria and never present with annular lesions [38]. Additionally ordinary urticarial lesions are more pinkish than darker reddish lesions of UV [38]. In addition, UV lesions tend to be located more on dependent areas of the body [38]. Serum-sickness is a type-III hypersensitivity reaction that develops for example against horse-serum diphtheria antitoxin and can present with urticarial lesions [59]. Serum-sickness like reaction is a similar clinical entity triggered by drugs or infections [59]. Urticaria multiforme presents with annular lesions and acral edema or angioedema, mostly triggered by viral infections [59]. Both are self-limited and have favorable long-term prognoses [59]. Acute infantile hemorrhagic edema is another self-limited disorder that should be remembered in differential diagnosis of hemorrhagic urticarial lesions in pediatric cases [59]. Henoch-Schönlein purpura can present with urticarial lesions and should be searched for especially in pediatric cases with renal and/or gastrointestinal and/or arthritic involvement [59]. Urticarial arthritis is a condition observed in HLA-B51 positive patients, presenting with arthritis, urticaria (lasting less than 24 hours), and facial angioedema [49]. Some of the patients may show a biopsy with leukocytoclastic vasculitis some only leukocytic infiltration without vasculitis [49]. Acquired angioedema should be differentiated from HUV associated with angioedema and both disorders have decreased complement levels. Pruritic urticarial papules and plaques of pregnancy is the main differential diagnosis when UV develops in the pregnancy, especially in the striae distensae [60]. Likewise erythema multiforme, bullous pemphigoid, sweet’s syndrome, and urticarial pigmentosa can be added to the differential diagnoses of UV [27].
\nAuto-inflammatory diseases are a group of rare hereditary monogenic disorders of innate immunity with presenting symptoms of fever and inflammatory, sometimes urticarial, skin lesions [3, 61, 62]. Auto-inflammatory diseases usually cause a familial life-long disease that starts in childhood in hereditary fever syndromes [62]. Auto-inflammatory syndromes cause flatter wheals and erythematous patches without surrounding flare and they last hours and even up to 24 hours and are accompanied by burning sensation rather than itching and they may be painful [62]. Lesions do not give any response to antihistamines and are associated with systemic symptoms of fever, fatigue, and arthralgia [62]. Very recently, vasculitis has been described histopathologically in three cases of auto-inflammatory diseases [61]. Hence, the clinician should take into account the rare possibility of auto-inflammatory associated vasculitis presenting with urticarial lesions and fever in the differential diagnosis of UV [61]. Some autoimmune disorders like SLE, Sjögren syndrome, dermatomyositis, or rheumatoid arthritis may present clinically with urticarial lesions [3]. Histopathological findings of UV are not specific in general and similar histopathological findings can be seen in SLE [42]. It is still unclear that HUVS is a similar disease to or a subtype of SLE [12, 28, 48, 63]. Both diseases share similar clinical findings and can present together [12, 28, 48, 63]. So when a patient is diagnosed as HUVS, he/she should also be evaluated for SLE [48]. Other systemic vasculitides may present clinically with urticarial lesions [3]. Rarely polyarteritis nodosa and Churg-Strauss syndrome may present clinically with urticarial lesions [3]. Some hematologic malignancies (lymphoma or gammopathies) and hematologic disorders (polycythemia vera and thrombocythemia) can also present clinically with urticarial lesions [3, 16, 17]. Other rare syndromes like PAPA, Blau, or Majeed syndromes can also present clinically with urticarial lesions [3].
\nIn any given patient with UV, if an underlying condition is present, it must be treated initially [2, 42]. Different degrees of clinical severity of the disease preclude proposal of any standard form of therapy [30]. Therefore, there is no universal therapy and variation in individual response to any form of therapy that exist [30]. In general, the more severe the systemic involvement (as in HUVS) is, the more challenging it becomes to treat the disease [42]. The most difficult patient to treat is the one who develops COPD or has established COPD in the setting of HUVS [2]. COPD in HUVS develops more frequently and most severely in patients who smoke, so patients should give up smoking and also avoid inhaling second-hand smoke [31]. One case has been reported to go into remission with an elimination diet [64]. This case may show the possibility of pseudoallergens’ role in the etiopathogenesis of UV and similar to chronic urticaria treatment a pseudoallergen-free diet can be tried in selected cases. Antihistamines are helpful for the symptomatic control of pruritus in all patients and may be sufficient for the therapy of mild cutaneous UV without systemic involvement [4, 30]. However, antihistamines do not affect immune-complex-mediated inflammation and hence do not alter the course of the disease [4]. Cinnarizine, an antihistaminic used for Meniere’s disease and car sickness, was found to be effective in UV patients [36]. A brief course of systemic corticosteroids may be useful to control intermittent exacerbations of UV, with both cutaneous and systemic involvement [4]. However, a dose of systemic corticosteroids up to 40 mg/day of prednisolone may be needed [30]. Long-term use is limited by the well-known side effects of corticosteroids and they should only be used in cases who are intolerant to or unresponsive to other alternative drugs [30]. A variety of alternatives to corticosteroids are used in the treatment of milder forms of UV [4]. These alternatives include indomethacin, colchicine, and dapsone that are commonly used in the clinical practice [4]. NSAIDs like indomethacin may help approximately half of patients with minimal disease [42]. Indomethacin use is usually discontinued or restricted by its gastrointestinal adverse effect potential, like upset stomach [4, 42]. In some unfortunate patients, NSAIDs can even cause UV or exacerbation of the existing UV [30]. Dapsone is a sulfone and shows more effectiveness than other alternatives in the treatment of UV [4]. Dapsone may work synergistically with pentoxifylline [4]. The mechanism of action of dapsone is poorly understood in the treatment of UV [4]. Before commencing on dapsone treatment, serum levels of glucose-6-phosphate dehydrogenase enzyme should be measured as deficiency of it results in severe hemolysis with dapsone usage [4]. Headache, nonhemolytic mild anemia and most importantly agranulocytosis may develop less frequently [4]. Hence, monitorization of complete blood count should be performed periodically in patients who use dapsone [4]. Patients having UV in the clinical setting of SLE or lupus-like disorder may have a more favorable response to treatment with dapsone [4]. Antimalarials like hydroxychloroquine have been reported to be effective in approximately 50% of patients with only cutaneous involvement [4, 30, 52]. Colchicine is an alkaloid that inhibits neutrophil chemotaxis, generation of lysosomes and stabilizes lysosomal membranes [4, 65]. It has clinical efficacy in selected cases of UV [65]. Reserpine is an alkaloid extracted from the roots of the plant Rauwolfia serpentine [66]. Reserpine was once used for the treatment of psychosis and hypertension [66]. It can be added to the antihistamines /corticosteroids in a dose of 0.3–0.4 mg thrice daily and reported to be helpful in majority of patients with UV [25, 66, 67]. If these alternative drugs do not get enough benefit or intermittent systemic corticosteroids do not control symptoms adequately then chronic systemic corticosteroid usage can be considered in milder forms of disease [4]. Higher dosage systemic corticosteroid treatment is necessary in the presence of hypocomplementemia or systemic involvement [4]. Systemic prednisone or equivalent is usually given at 1 mg/kg dose till clinical remission, later the dose could be slowly tapered [4]. Systemic corticosteroids could be tapered and discontinued without relapse in some patients [4]. However, many patients do experience disease relapse and need chronic corticosteroid treatment [4]. In the case of inadequate systemic corticosteroid response or when unacceptable corticosteroid adverse effects do occur than second line treatment choices should be considered, like azathioprine or cyclophosphamide [4]. In the resistant patients, systemic corticosteroids can even be effectively combined with dapsone, azathioprine, and cyclophosphamide [30]. In the chronic and resistant subset of patients, corticosteroid-sparing immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine A, or mycophenolate mofetil have been shown to be effective [4]. Azathioprine has been shown to be a useful adjunct to corticosteroids for stabilization of renal and pulmonary function [4, 68]. Methotrexate has usually inconsistent and disappointing results in the treatment of UV [4, 24, 33, 69]. Methotrexate is typically effective in inflammatory myositis associated with HUVS [70]. Favorable clinical responses have been achieved with cyclophosphamide in corticosteroid-resistant UV cases [4, 71]. Cyclosporine A has provided favorable clinical efficacy in the treatment of HUVS, including cases that are resistant to cyclophosphamide [4]. Cyclosporine A has been shown to improve respiratory involvement in HUVS patients with improvements in the forced expiratory volume in one second (FEV1), the diffusing capacity of the lung for carbon monoxide (DLCO) and regression of leukocytosis in bronchoalveolar lavage (BAL) [2]. Cyclosporine A has also been shown to be effective in renal involvement associated with HUVS [72]. Mycophenolate mofetil has also been shown to be efficacious in the treatment and maintenance of patients with HUV/HUVS [24, 73, 74]. Gold injections were tried and found to be effective in UV as in rheumatoid arthritis, but it is now a historical approach [75]. Plasmapheresis can provide rapid but temporary benefit in recalcitrant cases of UV [4, 76]. Plasma exchange has been shown to control symptoms rapidly during treatment but lesions recurred later in some patients [30, 76, 77]. High dose intravenous immunoglobulin (IVIG) also has been tried and shown to be effective in some recalcitrant HUVS cases [20, 78]. However, there are cases with inefficient response to IVIG [67, 79]. Rituximab can be used in refractory and/or relapsing or severe cases with prolonged duration of efficacy [46, 56, 80]. Anti-IL-1 blockage (anakinra, canakinumab) has shown promising results in the treatment of UV [81, 82]. However, these patients may have UV associated with auto-inflammatory diseases. A therapy-resistant SLE patient with UV lesions showed good response to IL-6 antagonist tocilizumab [83]. Omalizumab was used in a small number of NUV patients with success but some displayed a quick relapse following discontinuance [84, 85]. First line treatments used were determined to be mostly corticosteroids, hydroxychloroquine, and colchicine in decreasing order in a large retrospective study that involved only HUV patients [46]. Second and third line treatments given in this study were corticosteroids, hydroxychloroquine, and immunosuppressive agents in decreasing order [46]. In patients having hepatitis C infection, cryoglobulinemia and resultant UV, effective antiviral therapy (interferon-alpha and ribavirin) should be instituted [2]. Effective antiviral therapy has been shown to control HCV infection and cure UV in nearly half of these patients [2, 86, 87]. However, if the antiviral treatment is stopped the UV lesions do recur [87]. Angioedema may develop at any time in the course of UV [31]. If angioedema develops and involves larynx, the initial treatment may be epinephrine [31].
\nUV is a complicated disease and it has an unpredictable course [12]. An individual can have lesions for weeks to many years continuously or intermittently [12, 30]. The average duration of the disease was found to be 3 years and disease could last up to 23 years [30, 42]. Response of patients with UV to any given treatment is variable [4]. The course of the idiopathic NUV is favorable overall and patients usually do not develop any other diseases or mortality in the follow up [12, 30]. The course of HUV and HUVS may be less favorable [12, 30]. Patients with HUV may need an additional add-on therapeutic after about a median of 8 months duration [46]. Musculoskeletal, ocular, and renal disease usually responds to systemic treatment without any long-term severe consequences [14]. After adequate therapy serum complements increase to or near to normal values and anti-C1q antibody titers decrease [14]. However, serum C1q levels remained below normal values even in the presence of complete remission [14]. UV presents clinically in a spectrum of disease severity from NUV to HUV to HUVS [42, 46]. However, there is no finding to support the presence of any transition from one to another in follow up of these patients [42]. The main causes of morbidity and mortality are pulmonary manifestations like COPD, cardiac manifestations and laryngeal edema in patients with HUVS [14, 30, 31]. Precocious emphysema and COPD develop in patients with HUVS and especially in those patients who are moderate to heavy smokers [14, 88]. Onset of dyspnea heralds a poor outcome in HUVS patients with pulmonary involvement [14]. Treatment usually did not appear to alter the progression of COPD [14]. Of these HUVS patients with chronic or recurrent dyspnea, 55% die of respiratory failure [14]. In this subset of patients bronchogenic carcinoma can also be seen and adds to the overall morbidity and mortality risk [46, 88]. Cardiac involvement with pericarditis or valvulitis and significant valvular damage may develop in rare cases with HUVS and may be progressive and fatal [24, 33, 34, 46]. As cardiac involvement may cause significant morbidity and mortality and as its frequency is unknown, all patients should be evaluated [89]. Angioedema develops in 51% of cases with HUVS and may be life-threatening if it involves larynx [31, 46]. Pediatric and young adult patients (onset of disease before age of 30) may experience more renal involvement and show severe pulmonary complications and may have graver prognosis [89]. There may be significant morbidity resulting from involvement of other organ systems. Rarely vasculitis can affect optic nerve and retina and hence can threaten vision [90]. All UV patients need to be evaluated ophthalmologically as 15–20% of all UV cases may have ocular involvement in the disease course [90]. A patient with Muckle-Wells disease with associated UV developed sudden bilateral sensorineural hearing loss and had modest outcome following cochlear implantation [91]. Gastrointestinal involvement can lead to ischemic ulceration in the bowel [30]. Renal involvement can lead to renal insufficiency, this is especially common in pediatric cases and should be promptly treated [30, 89].
\nThere are other rare associated cutaneous findings in UV patients reported in the literature. A case with rapidly progressing acquired cutis laxa following involvement of the skin areas with lesions of NUV was reported [92]. A reported pregnant woman developed acquired reactive perforating collagenosis at the sites of resolved UV lesions 3 weeks following the onset and treatment of UV [19]. A reported UV case developed acquired hemophilia following 4.5 years of follow up [93]. Another reported NUV case first presented with acquired hemophilia and developed NUV and angioedema in the following 5 months [94]. Rarely inflammatory myositis can develop in HUVS cases despite ongoing immunosuppressive therapy [70]. Complement deficiency may lead to increased susceptibility to the infections with encapsulated bacteria, especially meningococcus [95]. As a result, a case of meningococcal meningitis that developed in a patient with HUVS was reported [95]. The course of the UV may accompany the course of underlying disease. A paraneoplastic NUV case was reported to clear with chemotherapy for underlying chronic lymphocytic leukemia and disease recurred with the recurrence of underlying hematologic malignancy [21]. Three women with UV were evaluated in a study including 29 systemic vasculitis patients with 51 pregnancies to search for the outcome of pregnancy in systemic vasculitis [96]. The authors have found that the patients with a diagnosis of systemic vasculitis may have exacerbation of the vasculitic disease during pregnancy or following delivery, may have more pregnancy related morbidity like preeclampsia and may have a lower median gestational age [96].
\nScented tea, also known as fragrant tea, is made from the flowers or leaves of plants. It is a type of reprocessed tea unique to China. It uses the properties of tea that make it good at absorbing odours and blends scented flowers and tea together. The tea absorbs the fragrance and then the dried flowers are removed using a sieve. The resulting scented tea has a strong fragrance and a bright tea drink. Scented tea has a long history of production. As early as the Song Dynasty, spices were added to green tea as a tribute to the emperor [1]. The processing technology of tea gradually matured during the Ming Dynasty and the scenting method of scented tea has since progressed [2]. The quality of scented tea is related to the scenting process. Mature scenting processes, such as moisturising continuous scenting, frying flower processes and innovative drying methods can be used to ensure that the scented tea maintains appropriate water content during the scenting process and improves the ability of the tea base to absorb the fragrance of the flowers. Chinese scented tea is mainly produced in the Guangxi, Fujian, Yunnan, Sichuan and Chongqing provinces. In 2021, the scented tea output in China was 2.917 million tonnes. Scented tea has been exported to Japan, the USA, Russia, Germany and other countries for many years and has a good reputation in local markets.
Scented tea contains various nutrients, such as proteins, amino acids, tea polyphenols, tea polysaccharides, vitamins and minerals. It also contains pigments, taste substances amino acids, catechins, caffeine and aroma substances. These substances not only improve the quality of scented tea but are also required for human physiological activities and contribute to the health effects of scented tea. Protein and amino acids are essential components of human metabolism. The water-soluble protein content of scented tea is around 2% and can be directly absorbed and used by the body through drinking the tea [3]. Scented tea is rich in amino acids, including theanine, glutamic acid and aspartic acid as well as vitamins. For example, jasmine scented tea contains 80–90 mg of vitamin C per 100 g of jasmine scented tea and can improve the immune system [4]. Scented tea also contains mineral elements, such as phosphorus, potassium, calcium, sodium, magnesium and sulphur as well as trace elements, such as iron, manganese, zinc, selenium, fluorine and iodine. In addition, the polyphenolic compounds, tea polysaccharides, caffeine and other components present in scented tea have good health effects on human physiological activities [5]. Scented tea also contains aromatic substances, including esters, alcohols and hydrocarbons, among which linalool, indole, benzyl alcohol and methyl salicylate are the main aroma components. These aromatic substances can aid digestion, relieve stomach pain and calm and regulate the nervous system [6]. Scented tea has the same refreshing effects as coffee due to its high content of caffeine and alkaloids, which are central nervous system stimulants. However, drinking coffee regularly may cause arteriosclerosis, whereas drinking scented tea can avoid this adverse effect. Scented tea contains polyphenols and vitamin C, which can effectively eliminate the adverse effects of caffeine. On the other hand, the caffeine in scented tea can promote gastric secretion, help digestion, enhance fat metabolism and effectively reduce body mass index [7]. Therefore, scented tea can also be used to promote weight loss. Scented tea contains a large amount of vitamin A, vitamin C and other trace elements that protect the eyes and have therapeutic effects on dry eyes caused by overuse of the eyes. Traditional Chinese medicine also commonly uses scented tea for the treatment of eye diseases [8]. Several cell and animal studies have shown that tea polyphenols, polysaccharides and pigments have significant anti-cancer and anti-tumour effects. The main anti-cancer pathways include inhibiting cancer cell proliferation, regulation of signalling pathways to induce apoptosis of cancer cells, inhibition of angiogenesis, inhibition of metastasis and infection of cancer cells and inhibition of tumour immune escape mechanism [9, 10, 11].
The pharmacologist Li Shizhen’s ‘Compendium of Materia Medica’ also records the health care effects of scented tea. The chemical composition and health functions of scented tea have been extensively studied over the past two decades to examine the mechanisms behind the health benefits of scented tea. The scientific community and mass media have gradually begun to pay attention to the beneficial properties of scented tea. For example, drinking scented tea is associated with anti-oxidant [12], anti-cancer [13], hypoglycaemic [14], hypolipidaemic [15], immunomodulatory [16] and neuromodulatory [17] effects. This chapter mainly reviews and discusses the health functions related to scented tea and the direction of future research and development.
Types of scented tea mainly include jasmine, lily, osmanthus, rose and honeysuckle, as shown in Figure 1.
Different types of scented tea. (a) Jasmine, (b) lily, (c) osmanthus, (d) rose, and (e) honeysuckle scented teas.
Jasmine scented tea is mainly produced in the Guangxi, Fujian, Sichuan and Yunnan provinces of China. It is a reprocessed tea made by blending tea with jasmine flowers. When brewed and consumed, its aroma is strong, fresh and refreshing. Jasmine scented tea generally uses green tea as the tea base. The choice of tea base is an important factor in determining the quality of jasmine scented tea. The aroma and taste of jasmine scented tea can be improved by making jasmine scented tea with green tea scraps of different particle sizes [18]. Different drying methods lead to changes in the surface and microstructure of the tea base, which in turn affect the quality of the finished jasmine tea. The emergence of vacuum freeze-drying technology has resolved this issue and the moisture content and overall quality of tea base have reached controllable conditions. Therefore, the quality of jasmine tea after scenting is better than that prepared by hot air drying [19].
Jasmine scented tea has physiological effects as well as significant health care properties. Studies have shown that jasmine scented tea can help obese people to reduce lipid levels and lose weight [20, 21]. Improved living conditions have led to women focusing more on ageing and skin problems. The anti-ageing and anti-oxidant health effects of jasmine tea also play an important role in the health benefits of jasmine tea. The polyphenols and pigments in jasmine tea have anti-bacterial effects. Gargling with the water extract of jasmine scented tea can resolve oral problems, such as oral ulcers and swollen gums.
Lily scented tea is mainly produced in the Anhui, Jiangsu and Guangdong provinces. Lily scented tea is prepared by processing fresh lily and green tea together, which retains the original biological activity factor of lily and has the fragrance of green tea. In addition to its strong aroma, lily has edible and medicinal properties. After scenting is complete, the flowers are mixed with tea, dried and packaged together, which improves the quality of scented tea and enhances its edible and medicinal value. Current methods of lily scented tea preparation include the treatment of tea billet, maintenance of flowers and the triple scenting of flowers. Finally, high-quality lily and dried tea greens are mixed for drying. This method can control the water content of lily scented tea, improve the quality and taste of lily scented tea and improve its medicinal value [22]. During the traditional drying process of flowers and tea, secondary drying reduces the fragrance of flowers and affects the quality of scented tea, while processing technologies, such as microwave drying or the use of desiccants, can greatly reduce the loss of floral fragrance [23].
Lily scented tea has high nutritional and medicinal values. While it is often made into desserts, people in the Guangdong region prefer to use it to make a tea drink to relieve coughing and sputum production. Lily scented tea tastes sweet and has no irritating taste. It moistens the lungs to stop coughing, clears away heart-burn and calms the mind. Lily scented tea is nourishing and medicinal and can be consumed all year round. It contains a variety of alkaloids, which have a preventive effect on leukopenia, increases the red blood cell count in the blood and has therapeutic effects on cytopenia after chemotherapy and radiotherapy [24, 25]. Lily scented tea can also improve the immune system and has preventive effects on a variety of cancers. The ‘Compendium of Materia Medica’ states that lily scented tea is a high-quality tonic and has properties similar to those of ginseng in tea.
Rose scented tea is mainly produced in the Guangdong and Fujian provinces in China. It is one of women’s favourite scented teas and is also the most common scented tea. Brewed rose scented tea exudes a refreshing aroma and refreshes the consumer. The quality of the finished product of rose scented tea is related to the processing technology. The type of rose and tea base used during the process directly affects the quality of scented tea. During the scenting process, freeze-dried roses are selected and mixed with green tea for secondary scenting. Airtight conditions are maintained during the scenting process to ensure an appealing drinking taste and aroma. Nutrients are not lost during scenting, improving the medicinal value [26]. The tea needs to be dried after scenting. Microwave technology can preserve the fragrance of the scented tea to a great extent and resolve issues such as dull colour and loss of aroma of the scented tea due to high temperature and humidity during drying using the traditional process [27].
Rose scented tea is a precious medicinal material and traditional Chinese medicine often uses rose scented tea with other traditional Chinese medicines to produce different formulas. Using rose scented tea to make wine can reduce blood lipid levels, improve vitality and improve skin texture [28]. Rose essential oil refined from rose scented tea can promote the development of male hormones and sperm and promote blood circulation and metabolism. Rose scented tea is also a commonly used a gynaecological Chinese medicine and has a significant effects in the treatment of gynaecological diseases [29]. Recent studies have shown that rose scented tea extract has anti-viral effects and has been used in the treatment of acquired immune deficiency syndrome and leukaemia and has achieved remarkable results.
Honeysuckle is a type of vine that is widely used in the pharmaceutical, food and chemical industries [30, 31, 32]. Honeysuckle scented tea is prepared by combining fried green tea and fresh honeysuckle in a sealer, separating the green tea and honeysuckle with gauze and stacking them in multiple layers to fully mix the honeysuckle and tea. Finally, dried honeysuckle and green tea are mixed and packaged. This process gives the tea a strong aroma and medicinal properties.
Honeysuckle is commonly used as a precious Chinese medicine. It is used to reduce fever and toxins, free the channels and improve circulation and has broad-spectrum anti-bacterial and anti-viral effects. More than 70% of cold medicines and anti-inflammatory patented Chinese medicines contain honeysuckle, which is known as ‘Chinese medicine antibiotics’ and ‘green antibiotics’. In addition to its medicinal properties, honeysuckle scented tea is used for beauty, weight loss and health care and has also been shown to protect and repair the body. Honeysuckle scented tea relieves heat stroke, sobers up individuals after consuming alcohol, clears the mind, relieves thirst, removes toxic substances from the body, lowers fat levels, reduces body weight, clears the skin, prevents ageing and increases longevity [33, 34, 35]. It can also lower blood pressure, lower serum cholesterol, increase coronary blood flow, prevent coronary heart disease and heart pain and inhibit the formation of cerebral thrombosis. Drinking honeysuckle scented tea can also improve the body’s resistance to hypoxic free radicals, delay ageing, improve microcirculation, remove peroxidised fat deposits and promote metabolism.
Polyphenols are an important component of tea, accounting for around 18–36% of the tea dry weight. Catechins are the main components of tea polyphenols, accounting for around 70–80% of the total tea polyphenols. Catechins can be categorised according to molecular structure into four types: epicatechin, epigallocatechin, epicatechin-3-gallate and epigallocatechin-3-gallate as shown in Figure 2. Tea polyphenols have strong anti-oxidant effects that are significantly greater than those of vitamins C and E, although they have synergistic effects with vitamin C and E, with anti-ageing effects [36, 37].
Structure of catechins EC, epicatechin; EGC, epigallocatechin; ECG, epicatechin-3-gallate and EGCG, epigallocatechin-3-gallate.
In addition to polyphenols, the chemical constituents of scented tea also include glycosides, flavonoids, lactones, coumarins, quercetin, terpenes and other compounds. Chemical studies on jasmine have shown that the main functional components of jasmine include nearly 100 compounds, such as volatile oils, fatty acids, glycosides, terpenoids, lignans and alkaloids [38]. According to the ‘Compendium of Materia Medica’, decoction of jasmine can be used to treat dysentery and abdominal pain and can also be used as an eye wash to treat conjunctivitis [39].
The chemical constituents of lily scented tea were examined by ethanol reflux extraction and the main components were found to be β-sitosterol, stigmasterol and emodin [40]. Among these, β-sitosterol lowers cholesterol, relieves cough and eliminates phlegm, inhibits tumour formation and inhibits skin ulceration. Sterols have high nutritional value and strong physiological activity and are commonly used in the pharmaceutical, cosmetics, animal growth regulators and food industries. Emodin can be used as a laxative and has anti-bacterial, anti-cough, anti-tumour and blood pressure lowering effects.
Studies on the chemical constituents of osmanthus scented tea show that the volatile components mainly include hexadecanoic acid, methyl docosatrienoate, camphor oil and isomenthone [41]. Studies have shown that the flavonoids in osmanthus scented tea have good anti-bacterial activity, especially against
Rose scented tea is rich in vitamins A, B and C and as well as amino acids, polysaccharides, alkaloids and other functional ingredients. The vitamin C content of roses is very high and can reach eight times that of kiwifruit, 20 times that of sea buckthorn and 700 times that of apples. Rose scented tea contains 16.33% protein and is rich in amino acids. Rose also contains a variety of unsaturated acids, including the essential fatty acids linoleic acid, linolenic acid and oleic acid, which together account for 99.75% of the total unsaturated fatty acids [43]. Rose is rich in dietary fibre, rose flavonoids and amino acids and can reduce blood lipids and blood sugar. It is also rich in trace elements including zinc, copper and manganese. These are important elements of superoxide dismutase and selenium, which is an important element of thiooxyreductase and glutathione peroxidase. These enzymes can improve the immune system and have good anti-oxidant effects [44].
The active components of honeysuckle mainly include phenolic acids, flavonoids, volatile oils and triterpenoid saponins, among which phenolic acids are important secondary metabolites in honeysuckle [45, 46]. Honeysuckle has good anti-oxidant activity due to its multiple phenolic hydroxyl groups in the structure [47]. Honeysuckle scented tea contains quercetin, luteolin, kaempferol, β-sitosterol, wogonin and other components, giving it fever-reducing and cleansing properties. It has also been shown to have preventive effects on coronavirus disease 2019 [48].
The anti-oxidant effects of scented tea can be attributed to the polyphenols in the tea and vitamins, flavonoids and phenols in the different scents. Ma et al. [12] found that jasmine scented tea contained large amounts of tea polyphenols compared with black and green teas and its anti-oxidant effects were greater that of vitamin C, as determined using the diphenyl-picrohydrazide method. Cong et al. [49] supplemented the diets of growing rats with 6% jasmine scented tea for 30 days and reported an significantly increased activity of anti-oxidant enzymes in the serum and liver. In addition, jasmine scented tea extract has significant anti-oxidant and anti-ageing effects on ageing mice [50]. A study on the anti-oxidant effect of healthy rabbits in vitro showed that the polar components of osmanthus tea can effectively remove superoxide ions in the body and lipid peroxidation of mitochondria in vitro [51]. Chen et al. [52] reported that 6 weeks of continuous gavage using rose scented tea in restraint stressed mice significantly increased the reduced liver catalase activity and glutathione content observed due to restraint stress and decreased plasma homocysteine levels by 20%. In addition, roses contain a large amount of vitamin C, which is a water-soluble vitamin with strong anti-oxidant activity that can effectively eliminate free radicals. After binding with free radicals, vitamin C can be transformed into dehydroascorbic acid and monohydroascorbic acid to eliminate free radicals, giving roses their anti-oxidant effect [43].
Scented tea has inhibitory effects on various cancers, such as liver, skin, stomach, lung, oral, breast, pancreatic and colon cancers [53, 54, 55], due to the presence of polyphenols and their oxidation products and caffeine. Tea polyphenols have strong anti-oxidant properties, scavenge free radicals in the body and can block the synthesis of carcinogens, such as ammonium nitrite. The inhibitory effects of scented tea on cancer are achieved via anti-oxidation, induction of apoptosis and regulation of gene expression. In addition, scented tea contains a large amount of chlorogenic acid and related derivatives, which have shown anti-cancer activity against U937 human histiocytic lymphoma cells, KB human oral cancer cells, MCF-7 breast cancer cells and WI38 lung fibroblast cells [56]. Chlorogenic acid can inhibit colon cancer by inducing the production of reactive oxygen species, lung cancer cells by affecting the expression of apoptosis-related genes and liver, oral, gastric, cervical and breast cancers [57, 58, 59]. Kawabata et al. [60] used azomethane to induce a rat model of colon cancer and found that ferulic acid could reduce the incidence of colon cancer in rats. Protocatechuic acid can reduce the enzyme activity of MCF-7, A549 non-small cell lung cancer cells, HepG2 human liver cancer cells, HeLa cervical cancer cells and LNCaP prostate cancer cells, effectively penetrate cancer cells, inhibit lactate dehydrogenase activity and damage the mitochondrial membrane potential and also inhibit MMP-2 secretion to prevent its metastasis in human gastric cancer AGS cells [61]. Studies have found that caffeic acid mainly exerts its anti-cancer effects by affecting the mRNA regulatory network and up-regulating levels of mitochondrial reactive oxygen species in tumour cells [62]. Studies have also shown that isochlorogenic acid A has an inhibitory effect on human ovarian cancer cells, skin melanoma cells, central nervous system tumour cells and colorectal cancer cells [63].
Diabetes is one of the most common chronic diseases seen in clinical medicine its the incidence has gradually increased in young people. The blood glucose levels of individuals fluctuate; however, stable blood glucose levels are an important evaluation index of individual physical health. Scented tea can improve the ability of vanadate to regulate blood glucose. Vanadate suspended in jasmine scented tea has hypoglycaemic effects and can stably and effectively maintain blood glucose at a normal levels within a few weeks [64]. Studies have shown that drinking jasmine scented tea significantly reduces blood glucose [18]. Starch (polysaccharide) in food is digested into oligosaccharides by salivary amylase and pancreatic amylase, converted to glucose by α-glucosidase in the small intestine and finally absorbed. Studies have found that osmanthus tea extract has an inhibitory effect on α-glucosidase [65]. The presence of phenolic compounds in honeysuckle scented tea extract was shown to reduce blood sugar levels in sucrose hyperglycaemic mice and an alloxan diabetes mouse model [66].
Caffeine in tea can reduce the concentration of triglycerides in blood and catechin can inhibit lipid synthesis. The comprehensive effects of caffeine, catechin, tea polysaccharide, cholestenone, inositol, folic acid and pantothenic acid in tea can prevent and inhibit obesity. Studies have shown that the effect of jasmine scented tea on weight control may be related to its ability to increase lipoxin levels [64]. Consumption of jasmine scented tea can prevent elevated blood lipid levels and atherosclerosis, reduce the content of molecular substances in plasma and protect organs, such as the liver and kidneys. A study on rose scented tea found that its lipid-lowering effect mainly comes from its high content of dietary fibre, rose flavonoids and various amino acids [67]. Rose scented tea is rich in dietary fibre, which cannot be converted to glucose in the human body, and has a low glycaemic index. It may be used as a common food for patients with diabetes. Dietary fibre can also combine with bile salts (metabolites of cholesterol), which are then excreted, effectively reducing the concentration of cholesterol in serum and further preventing and treating cardiovascular and cerebrovascular diseases. In addition, dietary fibre also promotes gastrointestinal motility, which can effectively prevent constipation and reduce the incidence of intestinal cancer. Lan et al. [68] examined the effects of rose extract on blood sugar and glucose tolerance in diabetic mice and found that both rose liquid extract and alcohol extract could effectively reduce blood sugar and improve glucose tolerance. A dose effect was seen and rose alcohol extract exerted a greater lipid-lowering effect than rose water extract. A previous study evaluated the lipid-lowering effects of water-extracted flavonoids from honeysuckle and found that they significantly reduced plasma triglyceride and plasma cholesterol levels in hyperglycaemic mice [69]. The mechanisms involved changes in the transcription and expression levels of insulin receptor substrate 1, low density lipoprotein receptor, apolipoprotein 1, fatty acid synthase and cholesterol regulatory element binding protein 2 in the liver of the mouse model. These studies indicate that the polysaccharides, amino acids and flavonoids contained in jasmine, rose and honeysuckle have lipid-lowering effects and that these active substances are likely to have synergistic effects with the polyphenols in green tea in reducing blood lipids.
The immune system provides resistance to disease. Researchers at the Fujian Institute of Traditional Chinese Medicine studied the immune function of scented tea on animals. Jasmine scented tea was shown to increase the number of white blood cells, lymphocytes and T lymphocytes in the blood [16]. Lin et al. [70] compared the effects of jasmine scented tea, traditional Chinese medicine (the main components are angelica, yam and liquorice) and compound tea (88.5% scented tea and 11.5% of traditional Chinese medicine) on the immune function of mice with acute renal failure. The results showed that 2.5% scented tea, 2.5% compound tea and 0.3% traditional Chinese medicine could significantly reduce the content of molecular substances in serum and significantly promote the proliferation of mouse spleen T and B lymphocytes and enhance the activity of mouse spleen lymphocytes. The study further showed that jasmine scented tea, traditional Chinese medicine and compound tea could enhance the immune function of the spleen in mice and jasmine scented tea and compound tea had more significant immune effects on mice. In addition, Li et al. [71] used ovalbumin sensitised mice as an immune response model to study the immunoregulation effect of aqueous extract of honeysuckle. Water extract of honeysuckle could alleviate the inflammation of intestinal villi in allergic mice, reduce the aggregation and degranulation of mast cells, increase the ratio of intact mast cells in the lamina propria, reduce the release of histamine in the intestinal tract of allergic mice, reduce levels of interleukin-4 and ovalbumin, reduce the ratio of interleukin-4/interferon-γ in allergic mice and inhibit transcription levels of interleukin-12 in peripheral lymphoid tissue mononuclear cells.
The aroma of scented tea can relieve depression and reduce anxiety and also improve concentration, relieve physical stress and improve work efficiency. Studies have shown that inhaling the aroma of jasmine scented tea can improve the rate of simple mental arithmetic by 10% and alleviate tachycardia [72]. Kyoko et al. [73] showed that inhaling the aroma of jasmine scented tea for 5 min can significantly reduce heart rate, making people feel calm and energetic. Another study reported that the aroma of jasmine scented tea contained (R)-(−)-linalool, which plays a sedative role in human autonomic nervous activity and emotional state. Li et al. [29] conducted a study on the intervention effect of rose scented tea on postpartum depression and found that rose scented tea could reduce the Edinburgh Postpartum Depression Scale score in patients with postpartum depression and alleviate related symptoms to varying degrees. Subsequently, Zhai et al. [74] conducted a comparative study on rose scented tea and sweet orange essential oil, which has sedative effects. Inhalation of rose scented tea and sweet orange essential oil using aromatherapy lamps significantly reduced blood pressure and heart rate and rose scented tea was better at relieving the systolic blood pressure. Scented tea contains high amounts of volatile substances, which together form the unique aroma of scented tea. Among these, hydrocarbons, alcohols, esters and phenolic compounds are volatilised after brewing and heating the scented tea. These substances are absorbed by the capillaries of the lungs and then transported to the whole body via the blood, relieving the muscles and brain cells of the body.
China has established a refined tea production system and is a leader in research into scented tea ingredients. Scented tea is used medicinally and as a foodstuff and drink. The health benefits of scented tea on the human body are well established. Advances in human nutrition and increased interest in physical health have led to increased attention about the nutrition and health benefits of food. Studies have shown that the polyphenols and flavonoids present in scented tea promote human physical health, which keeps the market share of scented tea in China high.
However, the health benefits of scented tea should not be overstated. Scented tea is a health drink, not a drug, and it regulates but does not cure the human body. In addition, attention should be paid to the application of chemical fertilisers and pesticides in the cultivation of flowers and tea as pesticide residues in scented tea may seriously affect its quality and safety. Attention should be paid to the selection of raw materials used in the preparation of scented tea. Fresh, plump flowers and tea are used as raw materials and the flowers and tea are processed in strict accordance with the scenting process. Finally, the health benefits of scented tea are not achieved by a single substance, but the synergistic effects of multiple chemical components, which should be considered comprehensively when using scented tea.
This work was supported by the Yunnan Provincial Natural Science Foundation (Grant No. 202101AT070038), Yunnan Agricultural joint project (202101BD070001-105), China Scholarship Council, and, as well as the Yunnan Provincial Youth top talent project (Grant No. YNWR-QNBJ-2020-166), Natural science foundation of Yunnan Provincial department of education (2022Y553) and Middle-age Reserve Talents of Academic and Technical Leaders (2019HB026) and the 111 project (D21027).
Writing-original draft, Bowen Liu; supervision, Jun Zhang, review & editing, Guanben Du, Shuduan Deng and Xiaojian Zhou.
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