Waldenström macroglobulinemia-induced bullous dermatosis.

BACKGROUND: Waldenström macroglobulinemia is a plasma cell dyscrasia of undetermined cause characterized by the monoclonal proliferation of lymphoplasmacytes in the bone marrow, lymph nodes, and spleen and elevated circulating levels and tissue deposition of monoclonal IgM produced by these aberrant cells. Rarely, cutaneous manifestations of this disease have been reported. OBSERVATIONS: We report the case of a patient with bullous dermatosis induced by Waldenström macroglobulinemia and demonstrate the subepidermal location of the separation and the presence of IgM and kappa light chains by immunoperoxidase, immunofluorescent techniques, and electron microscopy with immunogold staining. Immunoblotting revealed a strong band at the 290-kd area. CONCLUSIONS: The demonstration of the separation in the upper dermis at the site of IgM deposits suggests that these deposits may be an etiologic factor in this rare manifestation.

In three types of interface dermatitis, different patterns of expression of intercellular adhesion molecule-1 (ICAM-1) indicate different triggers of disease.

We found distinct patterns of intercellular adhesion molecule-1 (ICAM-1) expression in three diseases characterized by interface dermatitis with mononuclear infiltrates and keratinocyte cytotoxicity: lichen planus (LP), subacute cutaneous lupus erythematosus (SCLE), and erythema multiforme (EM). In LP, basal keratinocytes show strong ICAM-1 expression associated with a dermal infiltrate, but ICAM-1 expression in the rest of the epidermis is minimal. In SCLE, there is diffuse epidermal ICAM-1 expression, sometimes with accentuation on the cell surface of basal cells. In EM, there is strong basal cell expression of ICAM-1 with evident cell surface accentuation, and also pockets of suprabasal expression with cell surface accentuation. These patterns are associated with different factors that trigger cytokine release in different locations. Both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) produce greater relative ICAM-1 expression in basal keratinocytes than in more differentiated keratinocytes. In LP, the pure basal keratinocyte expression of ICAM-1 appears to be caused by cytokines, predominantly IFN-gamma, released by dermal lymphocytes. The pattern of ICAM-1 in SCLE corresponds to the pattern induced by ultraviolet radiation (UVR): diffuse epidermal ICAM-1 expression, sometimes with basal accentuation. Some individuals are "responders" to TNF-alpha or UVR, showing high levels of ICAM-1 expression following UVR or TNF-alpha stimulation in vitro or UVR stimulation in vivo. We propose that the pattern of ICAM-1 induction in SCLE is dependent on UVR-induced TNF-alpha release. EM is associated with apparent latent Herpes simplex virus, and Herpes simplex virus (HSV)-infected keratinocytes show enhanced ICAM-1 expression. We propose that in EM suprabasal ICAM-1 expression may be induced directly by HSV infection or indirectly through TNF-alpha release induced by HSV reactivation. Induction of ICAM-1 within the epidermis is stratified and individually variable. Basal keratinocytes show maximal induction of ICAM-1 expression due to innate sensitivity to TNF and IFN-gamma stimulation, and to location adjacent to dermal sources of cytokines. Suprabasal ICAM-1 can be induced by UVR and epidermal TNF-alpha release, and by factors such as viral infection. Different triggers of cytokine release and adhesion molecule induction may influence the different patterns of inflammation seen in diverse inflammatory skin diseases.

Subacute cutaneous lupus erythematosus.

Gilliam recognized subacute cutaneous lupus erythematosus (SCLE) as a lupus-specific eruption that identifies a unique subset of lupus erythematosus. These patients were noted to have prominent photoaggravated skin disease and often had musculoskeletal complaints, but generally did not develop significant systemic disease. SCLE patients were later found to have other distinctive features, including the frequent presence of anti-Ro antibodies, and enrichment for the human histocompatibility antigens (HLA) B8 and DR3. In the 13 years of published reports of SCLE patients following the initial study by Sontheimer et al (Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 115:1409-1415, 1979) a number of additional observations regarding SCLE patients have been made. These have included the recognition that SCLE may be associated with other rheumatic diseases, and that photoactive medications may induce lesions of SCLE. Areas of controversy concerning SCLE include conflicting studies regarding the histopathology of SCLE as compared to discoid lupus erythematosus (DLE), as well as the frequency of detection of anti-Ro antibodies in SCLE patients. Recent interesting studies of SCLE include a description of a unique pattern of immunoglobulin G (IgG) deposition on direct immunofluorescence, which may indicate the binding of anti-Ro antibodies to keratinocytes in vivo.

Clinical, histologic, and immunofluorescent distinctions between subacute cutaneous lupus erythematosus and discoid lupus erythematosus.

Subacute cutaneous lupus erythematosus (SCLE) was originally described and distinguished from discoid lupus erythematosus (DLE) on the basis of clinical examination of the skin, but subsequent reports have questioned the concept of SCLE as a marker of a unique subset of LE patients. We classified 27 lupus patients, on the basis of cutaneous exam, as having discoid lupus skin lesions, subacute cutaneous skin lesions, or systemic lupus erythematosus (SLE) without DLE or SCLE lesions. Clinical features most characteristic of SCLE rather than DLE were superficial, non-indurated, non-scarring lesions, and photosensitivity, with lack of induration being the single most helpful finding. Histologic examination of lesional skin showed a relatively sparse, superficial infiltrate in SCLE and a denser, deeper infiltrate in DLE. A distinctive pattern of staining with direct immunofluorescence, particulate epidermal IgG deposition, was found in seven of seven SCLE patients (all anti-Ro/SSA positive) and none of the other patients. This distinctive pattern can be reproduced experimentally when anti-Ro/SSA autoantibodies are infused into human skin-grafted mice. Particulate dermal-epidermal junctional staining was the pattern seen in the patients who did not have SCLE. Clinically defining SCLE as a superficial inflammatory form of cutaneous lupus (i.e., considering lesions to be DLE if they are indurated) results in a meaningful segregation of SCLE and DLE patient groups. The epidermal IgG deposits unique to SCLE provide independent evidence that the clinical findings that were used to identify the patient groups actually identify distinctive cutaneous lupus subsets. The observation that antibodies are present in a different location in the skin in SCLE than in DLE indicates that SCLE and DLE are likely to have different pathomechanisms.

Microscopic polyarteritis. Report of a case with cutaneous involvement and antimyeloperoxidase antibodies.

BACKGROUND: Microscopic polyarteritis is a systemic small-vessel vasculitis that primarily involves the kidneys but may also affect the skin and other organ systems. This unique vasculitis represents one of the vasculitides with antineutrophil cytoplasmic antibodies, usually of the perinuclear immunostaining pattern (P-ANCA, antimyeloperoxidase antibodies). The objective of this case report is to describe microscopic polyarteritis, the use of antineutrophil cytoplasmic antibodies, and the unique cutaneous histopathologic features of our patient. OBSERVATIONS: We describe a patient with clinical findings consistent with microscopic polyarteritis, the presence of antimyeloperoxidase antibodies, and a specific cutaneous leukocytoclastic vasculitis. This report further characterizes the histopathologic features by demonstrating that the anatomic location of the cutaneous vasculitic lesions is at the level of the dermal arteriolar vessels and postcapillary venules. CONCLUSIONS: Cutaneous arteriolar leukocytoclastic vasculitis may prove to be a histologic hallmark of microscopic polyarteritis when it presents in the skin. However, further case comparisons and histopathologic investigations are needed. The consequences of this systemic vasculitis, if not adequately treated, may be life threatening. Recognition of clinical features, use of antineutrophil cytoplasmic antibodies, and demonstration of a cutaneous arteriolar leukocytoclastic vasculitis may aid in the diagnosis and subsequent treatment of patients followed up by dermatologists for vasculitic ulcers.