Ultrastructural localization of immunoglobulin and fibrin in lichen planus

To demonstrate the exact localization of immunoglobulin and fibrin deposits in skin lesions of lichen planus, we employed the peroxidase-antiperoxidase technique, both light and electron microscopically. IgM is shown to be deposited preferentially in and on the cytoid bodies all over their cut surface in a typical stippled pattern, partly obscuring the characteristic fibrillar substructure. All other structures such as the basal lamina are devoid of IgM deposits. Fibrin (F) is also present in cytoid bodies but in a lesser amount; it is characteristically deposited on and along the basal lamina and its reduplications in the uppermost strata of the dermis. Our results indicate that IgM deposition in cytoid bodies occurs at a very early stage during the formation of these structures and that fibrinogen exhibits a specific affinity not only to cytoid bodies but also to basal lamina material.     

Demonstration of immune complexes in spontaneous and histamine-induced lesions and in normal skin of patients with leukocytoclastic angitis.

Clinical and laboratory observations have strongly suggested that leukocytoclastic angitis is an immune complex disease. Since immune complexes can be visualized as electron-dense deposits by electron microscopy (EM), this method was used in conjunction with direct immunofluorescence (IF) to determine whether complexes could be demonstrated in spontaneous lesions, and in uninvolved skin in which the vessels were made permeable by the local injection of histamine. Histamine-induced wheals were produced in the uninvolved skin of patients with active angitis. In the resulting wheal, EM studies revealed electron-dense deposits characteristic of immune complexes in postcapillary venules and direct IF studies demonstrated complement and immunoglobulins in the vessel walls. Neutrophils in varying stages of disintegration were present thereby reproducing the histopathologic changes of spontaneous lesions. EM and IF studies of nonmanipulated uninvolved skin also revealed electron-dense deposits and immune reactants in the vessel walls. Neutrophils were not present, however. This observation indicates that immune complexes are deposited in vessels before tissue damage ensues. Study of spontaneous lesions older than 24 hr revealed only fibrin by EM and no immune reactants by direct IF. In spontaneous lesions less than 24 hr old, electron-dense deposits and fibrin were seen by EM, and complement and immunoglobulins by IF. Histamine-induced wheals should be a useful device to investigate patients with disorders that have an immune complex pathogenesis.     

Heterogeneous disease: a child case of lichen planus pemphigoides triggered by varicella

Lichen planus pemphigoides (LPP) is a rare and controversial disease. It is characterized clinically by tense bullae arising both on lichen planus papules and on uninvolved skin, histologically by the demonstration of subepidermal bullae and by linear deposits of immunoglobulin G and C3 along the basement membrane zone on immunofluorescence of peribullous skin. Some authors consider LPP as the combination of lichen planus and bullous pemphigoid. Others think that it most likely encompasses a heterogeneous group of subepidermal autoimmune blistering disorders occurring in association with lichen planus. We present a child case that supports the heterogeneous condition of this disease triggered by varicella.     

Cytodiagnostic use of Feulgen-DNA measurements in cell imprints from the skin of patients with mycosis fungoides

In the present immunofluorescence study we report the occurrence of fibrin or related substances and of IgM in the upper part of the dermis in all forty lichen planus lesions examined. Different amounts of various complement components and fragments were located in the epidermal basement zone, and in the colloid bodies. IgG, IgM, IgA and fibrin were also found in the colloid bodies, sometimes together with albumin. The earliest pathological change, which was seen in perilesional skin and in clinically normal skin from sites of predilection, was the presence of colloid bodies and pigment containing macrophages in the upper dermis. Deposition of fibrin appeared to be another early sign, as it was discernible in areas devoid of inflammatory infiltrate. The possible significance of these findings is discussed.     

Histopathological discriminant criteria between lichenoid drug eruption and idiopathic lichen planus: retrospective study on selected samples

The lesions observed in 15 idiopathic lichen planus (ILP) skin biopsies were compared with those occurring in 15 clinically relevant lichenoid drug eruptions (LDE). Various histopathological features were taken into account. Statistical analysis of results showed that none of these can be considered as a significant criterium allowing a pathognomonic differential diagnosis between ILP and LDE. Nevertheless, a strong suggestion of drug etiology can be inferred when the following histopathological signs ('LDE-related criteria') are present: focal parakeratosis, focal interruption of the granular layer, cytoid bodies in the cornified and granular layers, present in more than 50% of LDE and never in ILP.     

Coexistence of lichen planus and bullous pemphigoid

A 43-year-old white man presented with a generalized eruption of lichen planus and tense blisters within the lichenoid lesions and also on clinically normal skin. Direct immunofluorescence (IF) studies revealed immunological and histopathological characteristics of lichen planus in the lichenoid lesions and of bullous pemphigoid in the bullous lesions, and indirect IF studies showed that the patient had circulating antibasement membrane antibodies. The coexistence of both disorders may indicate a possible link between the pathology in the junctional zone in lichen planus and the appearance of antibasement membrane zone antibodies and bullous lesions, respectively.     

Mixed Lichen Planus-Lupus Erythematosus Disease

Two patients are reported with clinical symptoms of systemic lupus erythematosus associated with centrally ulcerated hypertrophic plaques and lip lesions. Histological findings from various sites were features of both lupus erythematosus and lichen planus. An increase in acid mucopolysaccharides and a thickened basement membrane which were present in some biopsies were interpreted as lupus erythematosus. The deposition of immunoglobulins and fibrinogen seemed to favor lupus erythematosus but these findings may also be seen in lichen planus. Four possible interpretations of the findings are discussed. The term "mixed lichen planus--lupus erythematosus disease" may be appropriate for these patients.     

Bullous lichen planus developed on erythema ab igne

Lichen planus developed on erythema ab igne which was induced by repeated exposures to a stove. The clinical and histopathological features of the eruption were an admixture of typical lichen planus and erythema ab igne. Subepidermal bullae were also found on the lichen planus. Direct immunofluorescence tests revealed deposits of fibrin in the basement membrane zone and IgM in the colloid bodies. Indirect immunofluorescence studies detected no circulating antibodies against cutaneous structures in the patient's serum. This study indicates that repeated thermal exposure over a prolonged period may produce lichen planus lesions.     

Therapie des Lichen planus pemphigoides durch Acitretin und pulsweise verabreichtes Kortikosteroid

A patient with lichen planus pemphigoides first developed multiple pruritic papules and subsequently, tense blisters on trunk and extremities. Histopathologic examination of a skin biopsy demonstrated both the typical changes of lichen planus and subepidermal blisters as in bullous pemphigoid. Direct immunofluorescence microscopy revealed both cytoid bodies and linear C3 deposits at the dermal-epidermal junction. By indirect immunofluorescence microscopy on 1 M NaCl-split-skin, circulating autoantibodies labeled the epidermal side of the split. Immunoblot analysis showed binding of the antibodies to the cell-derived soluble 120 kD domain of the 180 kD bullous pemphigoid antigen and to a recombinant form of the immunodominant NC16A region of this protein. When treated with pulsed intravenous corticosteroids, the patient continued to develop new papules and blisters, but when oral acitretin was added, the skin lesions cleared. The immunoblot reactivity of the patient's autoantibodies well reflected disease activity, while the indirect immunofluorescence microscopy titers did not.     

Lesional keratinocytes express OKM5, Leu-8 and Leu-11b antigens in lichen planus

Biopsy specimens of involved and uninvolved skin were studied in 16 patients with lichen planus using murine monoclonal antibodies against several cell surface markers of effector and/or accessory cells of the immune system. In contrast to uninvolved skin, keratinocytes were found to express HLA-DR, OKM5, Leu-8 and Leu-11b antigens in all biopsies from involved skin. We demonstrate here for the first time the in vivo expression of several effector and/or accessory cell markers on keratinocytes in lichen planus.     

Immunoperoxidase evaluation of lichen planus biopsies for hepatitis C virus

Background Lichen planus is a papulosquamous dermatosis which has recently been linked to infection with hepatitis C virus. It is unclear whether or not viral antigens may be present in the cutaneous lesions of lichen planus.
Materials and methods Twenty-five paraffin-embedded samples of glabrous lichen planus were evaluated using immunoperoxidase staining for the presence of hepatitis C virions. Control tissues consisted of hepatitis C-infected hepatic tissue ( n = 2), normal hepatic tissue ( n = 2), normal human skin ( n = 1), and two cutaneous biopsies of lichen planus from persons known to be infected with hepatitis C.
Results The sections of hepatitis C-infected liver tissue stained positive for hepatitis C virions. The 25 biopsies of glabrous lichen planus, the two biopsies of lichen planus from hepatitis C patients, the two sections of normal liver, and the one normal skin sample all failed to take up the stain.
Conclusions Cutaneous lesions of lichen planus are more probably reactive to the underlying infection than a manifestation of skin involvement by this disease. This theory is supported by the histologic findings in a lichenoid drug eruption, which are virtually identical to those of idiopathic lichen planus. Insufficient sensitivity by the immunoperoxidase procedure used is a possible explanation for our results; however, it appears more probable that no virus exists at the sites of cutaneous involvement.     

Lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens

We describe a case of lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens. A 24-year-old man presented pruritic erythematous patches with occasional central blister formation on the face, neck, and trunk and erythematous hyperkeratotic patches on the elbows and feet for 10 months. Histopathological findings of the neck and plantar lesions were consistent with lichen planus. Direct immunofluorescence studies from both lesions showed a linear deposition of IgG and C3 and cytoid bodies along the basement membrane zone. Indirect immunofluorescence studies demonstrated circulating IgG antibodies deposited on the epidermal side of salt-split skin. Immunoblot analysis using epidermal extract showed that the patient's serum reacted with 180 kDa bullous pemphigoid antigen (BPAG2) and a 200 kDa antigen. The cutaneous lesions almost cleared with a low dose of prednisolone and acitretin.     

Coexistence of lichen planus and bullous pemphigoid (an immunofluorescence study of a "lichen pemphigoides") (author's transl)]

A 35 year old black man presented with a generalized eruption of lichen planus; subsequently tense blisters appeared within the lichenoid lesions and on clinically normal skin. Histopathological characteristics of lichen planus were present in the papules, and those of bullous pemphigoid were seen in the bullae taken from non-lichenoid skin. Direct immunofluorescence studies revealed immunological characteristics of lichen planus in skin and mucosal lesions of L. P. Bound IgG and beta1 C/beta1 A with tubular patterns were detected at the dermo-epidermal junction in all the skin fragments (clinically normal skin, bullous lesions lichenoid skin and mucous lesions). Indirect immunofluorescence studies showed at several intervals that the patient had circulating antibasement membrane zone antibodies (IgG; titres 1/50). This is the third published case in which immunofluorescence studies have established the "pemphigoid" nature of some bullous lichen planus. These findings are in favour of an immune disorder in lichen planus.     

IMMUNOFLUORESCENCE STUDY OF DRUG-INDUCED LICHEN PLANUS-LIKE LESIONS

Using an immunofluorescence technique, we investigated lesions of drug-induced lichen planus-like lesions from patients. In addition, a comparative study of idiopathic lichen planus from thirteen patients was made. Deposits of fibrinogen along the epidermal basement zone, IgM, and less often IgA, IgG, C₁q and C3 on the colloid bodies were found in drug-induced lichen planus-like lesions. Similar deposits of immunoglobulins and complements were noted in 2 of 3 lesions developed by successful provocation tests. Deposits of fibrinogen were also demonstrated in all 3 lesions. However, no circulating antibodies directed toward the epidermal basement zone or other skin components were detected. No elevation of circulating immune complex levels was noted. Immunofluorescence findings in drug-induced lichen planus-like lesions were essentially identical to those in idiopathic lichen planus. This indicates that both conditions share a common disease process.     

Paucity of immune complexes in skin lesions of lichen planus

The significance of deposition of immunoglobulin and/or complements at the dermoepidermal junction (DEJ) and civatte bodies in skin lesions of 15 histopathologically confirmed cases of lichen planus (LP) was evaluated. Civatte boides were seen in 6 (40%) patients while in 9 (60%) these were absent. IgM, IgG, IgA and C3 were seen within civatte bodies in 6, 3, 2 and 3 specimens respectively in various combinations. LP lesions of a shorter duration (one year or less) had civatte bodies while these were absent in those with disease of a longer duration (more than 1 year). Immune complex deposition was seen in only 2 patients. It is concluded that civatte bodies are of diagnostic importance in lichen planus lesions of a short duration only and immune complexes do not seem to play a significant role in its pathogenesis.     

PUVA-induced lichen planus pemphigoides

A 72-year-old woman had suffered from parapsoriasis en plaque (large plaque type) controlled by topically applied psoralen ultraviolet A (PUVA) therapy. The parapsoriasis lesions gradually disappeared, but numerous tiny red papules with pruritus appeared over the forearms and lower legs 120 days after starting PUVA therapy. These papules developed to form violaceous plaques. Histological findings demonstrated the characteristics of lichen planus. Two months later, tense bullae developed on the plaques and on uninvolved skin of the limbs. These were subepidermal, with linear deposits of IgG and C3 along the basement membrane zone (BMZ) in immunofluorescence of peribullous skin, and immunodeposits of type IV collagen along the floor of the bullae. We therefore, diagnosed lichen planus pemphigoides (LPP). Using systemic and topical steroid therapy, the lesions rapidly resolved and there has been no recurrence. This case suggests that the combination of basal cell injuries caused by chronic inflammation and PUVA therapy could expose BMZ components to autoreactive lymphocytes and induce LPP.     

Immunofluorescence abnormalities in lichen planopilaris.

BACKGROUND--Lichen planopilaris is believed to be a variant of lichen planus because both diseases have similar histologic features. However, as the clinical features of the two diseases differ, we conducted immunofluorescence studies to examine the relation between the two conditions more closely. OBSERVATIONS--Direct immunofluorescence was performed on scalp lesions of seven patients with lichen planopilaris. All had abnormal linear deposits of Ig restricted to the basement membrane zone of hair follicles. The deposits consisted of only IgG or IgA in five patients (70%) and of IgG in combination with other Igs in two patients (30%). Basement membrane zone deposits of fibrin were present in only one patient (14%) and were linear in appearance. There was no staining of ovoid bodies. These immunofluorescence abnormalities differ from those associated with lichen planus where basement membrane zone deposits of fibrin are present in almost all patients, where the basement membrane zone deposits are fibrillar in appearance, and where the deposits of Ig over ovoid bodies are common. CONCLUSIONS--The different appearance and composition of abnormal deposits of immunoreactants in lichen planopilaris and lichen planus suggest that the two conditions are different diseases.     

The specificity and cellular origin of phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity in psoriatic skin

Phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity has been found in psoriatic skin and in this study, PNMT-like immunoreactivity was investigated in the involved and uninvolved skin of six patients with lichen planus and four patients with lichen simplex. No PNMT immunoreactivity was observed in these diseases. Studies were carried out using cultured fibroblasts from two patients with psoriasis from uninvolved and involved areas of skin and from two controls using antibodies to PNMT, as well as antibodies to the chemical messengers somatostatin, substance P, parathyroid hormone and peptide histidine isoleucine amide. No immunoreactivity to these substances was found, and fibroblasts are unlikely to be the cellular origin of the PNMT-like immunoreactivity as seen in psoriatic skin.     

Lichen Planus: A Clinical and Immuno-Histological Analysis

Background:

Direct immunofluorescence examination is an important technique in the diagnosis of cutaneous inflammatory disorders including lichen planus, especially in clinically and histopathological doubtful cases.

Objective:

To study the diagnostic utility of intensity, number, and subtypes of positive immuno-reactants found in lichen planus.

Materials and Methods:

A detailed analysis of clinical as well as immuno-histological features of lichen planus cases was carried out.

Results:

The male to female ratio was 1:1.1. The largest number of patients was in 31-50 year age group. Itching was the most common presenting symptom. Papular lesions were seen in 53% cases. Remaining had hypertrophic (6), follicular (3) and mucosal (9) variants. Clinico-pathological discrepancies were observed in 3 patients. The characteristic histopathological changes including basal cell vacuolization, band-like lymphocytic infiltrate at dermo-epidermal junction were seen in all the biopsies while Civatte bodies were detected in 29% cases. The overall positive yield of direct immunofluorescence microscopy was 55%. Immune deposits at Civatte bodies and dermo-epidermal junction were detected in 47% and 8% of cases, respectively. Immunoglobulin M was the most common immunoreactant followed by immunoglobulin G.

Conclusions:

There was no correlation found between the number and intensity of Civatte bodies with clinical variants of disease and also between the number of positive immunoreactants and clinical severity of the disease. The frequency, number, and arrangement of Civatte bodies in clusters in the papillary dermis as well as multiple immunoglobulins deposition at the Civatte bodies on direct immunofluorescence of skin biopsies are important features distinguishing lichen planus from other interface dermatitis.     

An immunofluorescence study of primary anetoderma

Primary anetoderma (PA) has occasionally been described in association with lupus erythematosus (LE). The present study was performed to elucidate a possible causal link between PA and LE by the use of direct and indirect immunofluorescence (IF) methods. Two patients with PA were studied. Biopsy specimens were obtained from early inflammatory and atrophic anetoderma lesions and from the exposed and unexposed uninvolved skin of each patient. The pattern of immune deposits observed in one patient was indistinguishable from that which is often seen in systemic LE, and in the other patient from that which may be observed in chronic cutaneous LE. The direct IF study also showed fibrillar immune deposits in the dermis that resembled elastic fibres morphologically. The indirect IF study, however, failed to demonstrate anti-elastic fibre antibodies in the patients' sera. The results of this study and a review of the literature suggest that some cases of PA have direct IF findings similar to those of either chronic cutaneous or systemic LE. However, these findings, along with the serological findings, are insufficient to establish a diagnosis of LE in most of these PA cases.