Dr.MD.IMRAN KAZMI ASST PROF.DEPT OF DVL,KIMS

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Silvia Lawrence
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1 Dr.MD.IMRAN KAZMI ASST PROF.DEPT OF DVL,KIMS

2 Lupus erythematosus is a multisystem disorder whose spectrum runs from a relatively benign, self-limited cutaneous eruption to a severe, often fatal, systemic disease. It is the root designation for a diverse array of illnesses that are linked together by distinctive clinical findings and characteristic patterns of polyclonal B cell autoimmunity.

3 Some patients present with life-threatening manifestations of systemic lupus erythematosus (SLE); whereas others, who are affected with what likely represents the same basic underlying disease process, express little more than discoid lupus erythematosus (DLE) skin lesions throughout their illness.

In the 1940 s and 1950 s dermatologists first recognised that most of their patients with chronic,scarring, discoid lupus erythematosus lesions had few, if any,systemic findings, whereas those with

4 In the 1940 s and 1950 s dermatologists first recognised that most of their patients with chronic,scarring, discoid lupus erythematosus lesions had few, if any,systemic findings, whereas those with photosensitivity and/or malar erythema frequently had systemic disease. They also recognised a middle group in whom the cutaneous lesions were more transient than in patients of systemic disease but for whom the prognosis was not as poor as that for patients with SLE.

5 These patients were categorised as having subacute LE also called disseminated DLE or subacute disseminated LE. The classification of cutaneous subsets was stressed by Gilliam and his coworkers.

6 Gilliam proposed that patients be classified,according to the type of cutaneous disease present, into two groups: those whose disease is characterized by an interface dermatitis known as histopathologically LE specific those whose disease is not.

7 The most common form of CCLE, a classic DLE skin lesion, is present in 15 to 30 percent of SLE populations selected in various ways. Approximately 5 percent of patients presenting with isolated localised DLE subsequently develop SLE. It has been suggested that SLE is sevenfold more common than DLE.

8 The cause(s) of and pathogenetic mechanisms responsible for LE-specific skin disease are not fully understood. The pathogenesis of LE-specific skin disease is inextricably intertwined with SLE pathogenesis.

9 An attractive contemporary model of SLE pathogenesis describes four theoretical temporally sequential phases that are prerequisite for the clinical expression of this disease. These phases are the inheritance of susceptibility genes, induction of autoimmunity, expansion of autoimmune processes, and immunologic injury

10 The first phase can be thought of as a susceptibility phase involving the inheritance of genes that confer predisposition to SLE. The genetic association between LE-specific skin disease and serologically determined major histocompatibility (MHC) class II DR specificities is well known

11 The second phase of SLE pathogenesis or the induction phase involves the initiation of autoimmunity characterized by the appearance of autoreactive T cells that exhibit the loss of selftolerance This third or expansion phase seems to involve progressive augmentation of the autoimmune response and has features of an antigen-driven response

12 The last and perhaps clinically most relevant stage that heralds the onset of clinical disease is that of immunologic injury. Much of this phase can be attributed to the action of autoantibodies and the immune complexes they form, which may cause tissue damage by means that include direct cell death, cellular activation, opsonization, and the blocking of target molecule function

13 Significant increases of HLA-B7, -B8, -DR2, - DR3, and -DQA0102 and a significant decrease in HLA-A2 have been reported for patients with DLE.

14 Ultraviolet light is probably the most important environmental factor in the induction phase of LE-specific skin disease. UV light could uncover an already established autoimmune state by triggering autoantigen release from an injured keratinocyte.

15 It is important to distinguish among the subtypes of LE-specific skin disease, because the type of skin involvement in LE can reflect the underlying pattern of SLE activity. In fact, the designations acute, subacute, and chronic, in regard to cutaneous LE, refer to the pace and severity of any associated SLE and are not necessarily related to how long individual lesions have been present

Lupus Panniculitis/Profundus 4.Mucosal A.

16 Chronic Cutaneous LE 1. Classical discoid LE A.Localised DLE B.Generalised DLE 2. Hypertrophic or Verrucous DLE 3.Lupus Panniculitis/Profundus 4.Mucosal A.Oral B.Conjunctival C.Nasal D.Genital 5.LE Tumidus/Papulomucinous 6.Chilblain LE 7.Lichenoid DLE(LE/LP Overlap)

17 The DLE lesion is characterised by erythema ; telangiectasia; adherent scale, which varies from fine to thick; follicular plugging; dyspigmentation; and atrophy and scarring. The lesions are usually sharply demarcated and can be round, thus giving rise to the term discoid.

of the nose, ears, sides of the neck and scalp.

18 Face is most commonly affected, circumscribed/discoid type (most frequent)occurs particularly on the cheeks, bridge of the nose, ears, sides of the neck and scalp. Lesions: Bilateral(although not necessarily symmetrical) or unilateral.

19 The presence of scarring and/or atrophy is the characteristic that separates these lesions from those of sub-acute cutaneous LE (SCLE)

20 Lesions on the ear lead to considerable atrophy and scarring.

21 Lesions occur as well-defined erythematous patches, varying in size from a few mm to cm. There is adherent scale in many cases, and when this is removed its undersurface shows horny plugs which have occupied dilated pilosebaceous canals.

22 This is called as tin-tack or carpet-tack or cat tongue sign. It can also be seen in localized pemphigus foliaceus.

23 Alopecia occurs in the scalp lesions in approximately onethird of patients, and is usually permanent

24 Patients with localized DLE have lesions located solely on the head,neck or both. This subset represents about one half of the chronic cutaneous LE population These patients differ from those with widespread DLE in a no of ways.

25 Those with localized disease rarely are among the subset of DLE-SLE. They have fewer manifestations that suggest systemic disease,and they less frequently demonstrate a positive antinuclear(ana)titer or leucopenia. It appears that the rare patient with DLE who progresses to develop more of the criteria for SLE is generally not in the localized DLE subset

26 Lastly,those patients with disease localized to the head and neck will frequently(roughly 50%)have a remission, whereas in those with widespread involvement, the disease rarely becomes clinically inactive(less than 10%) Thus it seems that it is prognostically worthwhile to separate the patients with localized DLE and those with widespread DLE into different subsets.

27 HYPERTROPHIC/VERRUCOUS LUPUS ERYTHEMATOSUS: It s a unique subset in which an unusual lesion occurs. The thick adherent scale is replaced by massive hyperkeratosis,and the lesions look like warts or squamous cell carcinomas These lesions usually occur in the setting of other,more typical DLE lesions.

28 Its an exaggerated proliferative epithelial response, Seen in 2% of patients with chronic cutaneous LE, Manifests as verrucous-appearing lesions. Clinically, two types of lesions have been reported in this subset of LE.

29 Lesions may simulate lichen planus or keratoacanthomas. The presence of lesions typical of DLE elsewhere is a helpful clue to the diagnosis. These patients tend to have chronic disease to have little in the way of systemic symptoms or abnormal lab findings,and to be extremely difficult to treat with conventional therapy.

The lesions of DLE can occur on the palms and/or soles. The frequency of this subset is low,and there is no specific clinical or serologic correlation.

30 The lesions of DLE can occur on the palms and/or soles. The frequency of this subset is low,and there is no specific clinical or serologic correlation. These patients can have chronic nonsystemic disease,or the lesions can be present in patients with SLE. Palmar and plantar lesions are often difficult to treat.

32 Oral DLE is histopathologically and clinically similar to cutaneous DLE These lesions are different from the oral and nasal ulcerations that occur in SLE Those that occur in the patient with SLE are associated with active systemic disease and are histopathologically nonspecific.

33 Typical lesion on buccal mucosa

34 DISSEMINATED DLE Seen on trunk and limbs, or may be localized to other body sites. Lesions on the dorsa of the hands, palms or toes- 6% of patients.

35 This occurs almost always in women, The appearance may be indistinguishable from the papulosquamous type of SCLE but scarring occurs in most patients. This variety tends to be persistent, resistant to therapy and associated with severe psychological upset.

36 Localized cribriform scarring occurs, particularly on the face

37 More frequently, a thin white scarred area, often with a slightly raised, red border or zone of hyperpigmentation, remains.

38 Wide follicular pits, sometimes containing scale or blackheads, occur mainly in the concha or triangular fossa of the ear. They occur in up to one-third of cases of DLE but they also occur in SLE.

39 Lupus tumidus is characterized by erythematous to violaceous plaques or nodules,usually on sunexposed surfaces These patients rarely have antibody abnormalities

40 It is a dermal form of LE without much surface changes. Tumid lesions may occur, in which the tissues are swollen, brawny, warm and tense. The surface shows a reddish, mottled appearance resulting from scarring. This type of lesion may be large and involve the whole of one cheek, or even the whole of a limb.

41 The pathology reveals an increase in mucin and a periappengeal and perivascular dermal infiltrate composed of lymphocytes,but there is little if any change at the dermal epidermal interface.

42 LEP is a lobular panniculitis that occurs rarely in patients with DLE or with SLE LEP is often chronic,and it can lead to cutaneous and subcutaneous atrophy and occasional ulceration.

43 The cutaneous infiltrate occurs primarily in deeper portions of the corium. With only microscopic epidermal changes, giving rise to firm, sharply defined nodules, lying beneath clinically normal skin

44 The DLE-SLE subset defines a small group of patients(5-10%)who by nature of their selection,have systemic disease in association with scarring cutaneous disease. Patients whose disease progresses from purely cutaneous disease into this group are characterised by widespred DLE,the presence of clinically appreciable periungual telangiectasias,persistent elevated ESR,leucopenia,and positive ANA titers

45 Patients in this group may have DLE alone at the onset,dle with symptoms and signs,or systemic disease without cutaneous lesions The time frame is variable,but most of the patients in this group develop the criteria for SLE within 1-3 years of diagnosis.

46 These patients with DLE-SLE rarely have renal disease, and even when they do so,it is most often transient and mild. DLE-SLE is a distinct LE subset because of its relatively benign, albeit chronic,course.

47 PATHOLOGY. Various clinical types of LE show an essentially similar histological picture, and the subsets of LE cannot be easily distinguished histologically. The salient features are as follows:

48 IgG, IgA, IgM and Complement at the DEJ, in skin lesions > 6 weeks(80% of patients). Homogeneous, granular or thready patterns occur, but the deposition is usually homogeneous in older lesions. They are more frequent on the face and in untreated lesions, but are rare on the trunk, and decrease after treatment with topical corticosteroids. They do not occur in uninvolved skin, unlike the majority of cases of SLE.

49 Positive lupus band test. Granular deposits of immunoglobulin G in the basement membrane zone on direct immunofluorescence of lesional skin.

50 Immunoreactants are also found in oral mucosa and the conjunctiva. C1q deposits are found in 29% of patients with IF positive DLE, compared with 90% in SLE, and the presence of such deposits implies an increased risk of eventual systemic disease.

51 T-cell counts are significantly lower than in controls, although B cells are not reduced. Kidney biopsy has shown silent lupus nephritis in patients with hypocomplementaemia.

52 SLE: The cutaneous lesions may be very similar, although patients with DLE of the face usually show more scaling, pigmentary disturbances, atrophy and scarring. In those with extensive DDLE, positive antibodies and mild systemic symptoms, it can be difficult to fit the patient into a precise diagnostic category, But patients may fulfil the ARA criteria for the diagnosis of SLE

54 MORPHOEA OR LICHEN SCLEROSUS: Annular atrophic plaque variety of DLE LP: Lesions on the lips, tongue, scalp and buccal mucosa may be confused with lichen planus.

56 CONTACT ECZEMA, SEBORRHOEIC ECZEMA AND PSORIASIS: The history and the presence of lesions elsewhere should exclude them LUPUS VULGARIS: Lesions occur at an early age, Are rarely symmetrical, May be ulcerated, Show characteristic apple-jelly nodules.

57 Lupus vulgaris of the face with lesions resembling discoid lupus erythematosis

59 NECROBIOSIS LIPOIDICA: Can have facial lesions like DLE. ROSACEA: The rosaceous type of LE can usually be differentiated from true rosacea by the absence of pustules and the histology.

60 PMLE: As many as 65% of patients with cutaneous LE have symptoms indistinguishable from those of PLE

61 The untreated skin lesions of DLE tend to be persistent. With treatment, the more tumid lesions with little scaling may clear completely in the course of a month or two. Longer standing lesions with much scaling and some scarring are slower to remit.

62 Scarring is found in 57%,Scarring alopecia in 35%,Pigmentary abnormalities 35%. Areas of activity at the edge of such scars may take years to settle. Complete remission (in years years) in 50%. Lack of remission are related to Raynaud s phenomenon, scalp involvement and chilblain-like lesions

63 Risk of developing overt SLE is only approximately 6.5% (Despite the fact that over half of patients have haematological and serological abnormalities). The risk is higher in patients with disseminated DLE (22%) than in DLE confined to the head and neck (1.2%). Females developing DLE before the age of 40 years, with HLA-B8 in their histocompatibility type, have an increased risk of converting to SLE

64 GENERAL MEASURES: Excessive exposure to sunlight and they should be avoided. A sunscreen should be prescribed. Camouflage by covering creams.

65 Topical therapy can frequently control and sometimes clear lesions without systemic treatment. More potent steroids are more effective. The efficacy in resistant cases may be enhanced by applications of steroid creams under plastic occlusion.

66 Intralesional corticosteroid injections are helpful in resistant cases, even on lips, mouth and ears. Multiple and repeated injections may be required.

67 Intralesional chloroquine has been tried with limited success. Interferon-α (IFN-α) has also been used intralesionally. Among other local measures, Cryotherapy, Surgical excision, Painting small lesions with Trichloracetic acid and Local laser therapy may be helpful. The carbon dioxide laser, and both the pulsed-dye and argon lasers may be valuable for telangiectatic LE.

For patients with severe, extensive or scarring disease, particularly affecting the scalp, oral prednisolone is often the most helpful initial treatment.

68 For patients with severe, extensive or scarring disease, particularly affecting the scalp, oral prednisolone is often the most helpful initial treatment. A dosage of 0.5 mg/kg, rapidly tapered over 6 weeks, is quickly effective, minimizes scarring, and allows the slower acting agents such as antimalarials to work.

69 Chloroquine sulphate is equally effective, usually at a dosage of 200 mg twice daily, but hydroxychloroquine is used first because side effects, particularly eye toxicity, are less likely provided that the dosage limitations of 6.5 mg/kg lean body weight are adhered to.

70 Methylprednisolone mg/day for 2 or 3 days, given as intravenous pulse therapy, may help resistant lesions. Hydroxychloroquine, initially at 200 mg twice daily, reducing to 200 mg/day once a response is achieved.

71 Most patients who are going to respond to antimalarials usually do so within 6 weeks. Eye check up before starting the treatment is important. Approximately 60 75% of all patients are helped by antimalarials. Hydroxychloroquine appears to be safe in pregnancy.

72 For cases not responding to topical steroids, antimalarials and sunscreens, oral thalidomide has proved remarkably effective in suppressing lesions, and also in the treatment of chilblain LE. 100 mg/day is effective dose. Short courses are preferable because of the risk of polyneuropathy and the teratogenic effects.

73 When all of the above have failed in patients with severe and persistent disease, other forms of systemic treatment may be used. Intravenous pulses of cyclophosphamide may be used, usually at a dosage of 10 mg/kg, at 3 4 weekly intervals.

74 It is usually given in combination with intravenous methylprednisolone. Most recently, the biological agents like Efalizumab have been used.

75 THANK YOU

Cutanous Manifestation of Lupus Erythematosus. Presented By: Dr. Naif S. Al Shahrani Salman Bin Abdaziz university

Cutanous Manifestation of Lupus Erythematosus Presented By: Dr. Naif S. Al Shahrani Salman Bin Abdaziz university A 50-year old lady, who is otherwise healthy, presented to the dermatology clinic with