Acquired bullous dermatosis associated with IgA multiple myeloma: a case report

We present the case of a patient with IgA paraprotein who developed hemorrhagic subepidermal vesicles and bullae with numerous neutrophils. Direct immunofluorescence test (DIF) showed weak deposits of IgA lambda paraprotein at the dermal–epidermal junction and at the intercellular level in the basal layer of the epidermis, and stronger deposits in a perivascular and diffuse pattern in the dermis. Indirect immunofluorescence (IIF) test revealed the presence of circulating IgA lambda antibodies reacting with the intercellular space of monkey and guinea pig esophagus and human skin. A blood test revealed an IgA lambda paraprotein and multiple myeloma stage I(0) was diagnosed in a later hematological study. Dapsone was prescribed and cutaneous lesions improved. This is the second report of subepidermal vesicles and bullae with dermal deposits of IgA paraprotein appearing prior to diagnosis of an IgA multiple myeloma, and it is a unique case with circulating IgA lambda antibodies reacting with the intercellular space of epithelia. Barnadas MA, Gelpí C, Martínez L, Curell R, Martino R, Alomar A. Acquired bullous dermatosis associated with IgA multiple myeloma: a case report.     

Multiple myeloma presenting as a novel mucocutaneous eruption

A 71-year-old woman presented with exquisitely tender mucosal erosions, a diffuse polymorphous eruption, and night sweats. Workup revealed multiple myeloma with a monoclonal IgG-kappa paraprotein in the serum. Her severe oral involvement was suggestive of paraneoplastic pemphigus, but direct and indirect immunofluorescence tests were negative. A skin biopsy showed spongiosis and a sparse perivascular lymphocytic infiltrate, with occasional CD8-positive lymphocytes in the epidermis. Her lesions improved with intravenous immune globulin. Immunohistochemical staining on the formalin-fixed biopsy specimen was strongly positive for IgG and IgG-kappa in an epidermal "chicken-wire" pattern, but negative for IgG-lambda. Her pulmonary tissue stained negative for IgG-kappa, suggesting clinical relevance of the myeloma paraprotein in her epidermis. To our knowledge, this is the first report of a multiple myeloma patient with such an eruption.     

Immunoglobulin A pemphigus associated with immunoglobulin A gammopathy and lung cancer

Immunoglobulin (Ig)A pemphigus is a rare disease marked by a vesiculopustular eruption characterized by intercellular IgA deposition in the epidermis. It has clinical and histopathological heterogeneity and encompasses two subgroups: subcorneal pustular dermatosis type and intraepidermal neutrophilic IgA dermatosis type. IgA pemphigus has been rarely associated with monoclonal IgA paraprotein, myeloma and B-cell lymphoma in the past. We report the first case, to our knowledge, of a 47-year-old male patient with a subcorneal pustular dermatosis type of IgA pemphigus associated with IgA gammopathy and lung cancer.     

Multiple hyperkeratotic spicules and myeloma

We report the case of a 58-year-old patient with multiple myeloma with a monoclonal gammopathy of the IgG type, who developed a striking eruption characterized by multiple hyperkeratotic spicules of the face, nose and scalp. Light-microscopic studies revealed a follicular orthohyperkeratosis, while direct immunofluorescence microscopy remained negative. Hence, our patient presented features characteristic of a rare distinctive disorder associated with an underlying paraprotein or multiple myeloma, paraneoplastic hyperkeratotic spicules.     

Scleredema adultorum associated with IgG-kappa multiple myeloma–a case report and review of the literature

The coexistence of monoclonal gammopathy with scleredema is an already known but unusual finding. However, the association of scleredema with multiple myeloma has only rarely been reported. A case of widespread longstanding scleredema is presented in which the finding of monoclonal gammopathy subsequently progressed to oven IgG-kappa multiple myeloma. From a review of the literature, it was concluded that scleredema patients having monoclonal gammopathy with or without multiple myeloma, share a number of clinical and laboratory features: (1) a widespread long-standing eruption; (2) no preceding upper respiratory tract infection and usually without accompanying diabetes mellitus; (3) most commonly identified paraprotein is IgG having a kappa light chain. It is suggested that scleredema should be included in the list of diseases related to monoclonal gammopathy, the latter either denoting monoclonal gammopathy of undetermined significance or representing an already existing or incipient multiple myeloma.     

Sweet syndrome in multiple myeloma: a series of six cases

BACKGROUND: Sweet syndrome (SS), a paraneoplastic syndrome characterized by fever, neutrophilia, multiple erythematous painful plaques, and a dense dermal neutrophilic infiltration, has a known association with hematologic malignancies such as acute myelogenous leukemia. However, no clear association with multiple myeloma (MM) has been reported. MATERIALS AND METHODS: Pathology reports of the 2357 patients with multiple myeloma at the University of Arkansas for Medical Sciences were reviewed to retrieve cases who had developed SS. Cytogenetic studies and immunoglobulin secretory status were retrieved. Five cases of SS in MM and 25 cases of SS in patients without MM underwent syndecan-1 immunohistochemistry. OBSERVATIONS: Six cases of SS occurring in the setting of MM showed a predominance in patients secreting IgG paraprotein. Five of the six patients received granulocyte-colony stimulating factor while the sixth received granulocyte-monocyte-colony stimulating factor. Fifty percent showed a non-specific cytogenetic anomaly. CONCLUSIONS: There is no specific cytogenetic anomaly associated with SS in the setting of MM. This paraneoplastic syndrome may be secondary to elevated levels of granulocyte colony stimulating factor (G-CSF), possibly with a component of enhanced sensitivity to endogenous G-CSF. The immunoglobulin secretory status parallels that seen in MM with cutaneous involvement, but IgG secretors may be at an increased risk of developing SS compared with their counterparts who secrete other immunoglobulins.     

Linear IgA disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD285 and a dermal 180-kDa protein

BACKGROUND: Linear IgA disease (LAD) of adults and children is mediated by IgA antibodies that target proteins of the epithelial adhesion complex. Most studies have concentrated on the epidermal-associated antigens; the dermal antigens remain unresolved. OBJECTIVES: To determine the dermal antigen repertoire of IgA and IgG antibodies in LAD. METHODS: Immunoblotting was carried out on salt-split and urea-extracted dermal skin extracts with IgA antibodies (63 adult and 34 childhood sera) and with IgG antibodies (49 adult and 18 childhood sera). RESULTS: Antigens were identified by IgA (61%), IgG (27%) and by both antibody isotypes (19%). LAD285 and an antigen of 180 kDa were the major dermal antigens identified, and antigens of 230 kDa, collagen VII and a protein under 100 kDa were identified less commonly. IgA autoantibodies from adults bound single antigens more frequently than multiple antigens; from children they bound single and multiple antigens equally. The binding of multiple antigens was, however, more common in children than adults. The IgG response was weaker. The 180-kDa antigen was the main IgG dermal target, and with a single exception, IgG autoantibodies targeted single antigens. CONCLUSIONS: There was an IgA and IgG response to dermal antigens in LAD; however, the dual antibody response was limited. The antibody response to LAD285 and a 180-kDa antigen (probably BP180) suggests that intermolecular epitope spreading of the antigens associated with the extracellular matrix/dermal components of the basement membrane contributes to the immunopathology of the disease. The restricted IgG response suggests that dermal-binding IgG autoantibodies are not pathologically significant.     

Subcorneal pustular dermatosis and IgA myeloma

The authors describe a new case of subcorneal pustular dermatosis associated with IgA myeloma. The significance of this association is unknown, but it seems to be more than a coincidence. The case described is particular, because the interval between skin eruption and first symptoms of myeloma is very long (27 years), and palms and soles are involved.     

In vitro synthesis of paraproteins in pathological skin

Two cases are reported, one of multiple myeloma and the other of erythrodermia (malignant reticulosis?), the former associated with a Bence-Jones paraprotein and the latter with IgM paraproteinemia. With an in vitro culture technique and/or the immunofluorescence method it could be demonstrated that the paraprotein present in the serum was synthesized not only in the bone marrow but also in the lesional skin.     

Extensive haemorrhagic-bullous skin manifestation of systemic AA-amyloidosis associated with IgGlambda-myeloma

In an 86-year-old woman with a multiple myeloma of the IgG lambda subtype a coinciding systemic amyloidosis manifested as a macroglossia, diffuse alopecia and generalized cutaneous involvement. The skin was affected by milium-like papules, petechial haemorrhages and an increased tissue fragility with subsequent blister formation. The typical histology and immunohistology pattern revealed large intradermal amyloid masses, reacting positively with anti-amyloid A antibodies, which surrounded cuff-like dilatated blood capillaries. The abundance of these amyloid deposits led to significant deflexibilization and fragility of the capillaries and the dermal matrix eventually resulting in the haemorrhagic-bullous eruptions. The peculiar feature of the present case is the intensity of bullous-haemorrhagic skin damage due to amyloid A deposition without any detection of cutaneous IgGl as the myeloma-derived paraprotein assumed to be causative for the development of systemic AA amyloidosis.     

Pyoderma gangrenosum associated with nasal septal perforation, oropharyngeal ulcers and IgA paraproteinemia

We report a case of pyoderma gangrenosum (PG) associated with nasal septal perforation, pharyngeal ulcers and IgA paraproteinemia. A 28-year-old woman first developed painful undermined ulcers on her perianal, inguinal and axillary areas when she was 22 years old. Histological findings from the cutaneous ulcers showed dermal and epidermal infiltrate of neutrophils, which was compatible with PG. Laboratory examinations did not detect any associations of systemic diseases other than polyclonal IgA paraproteinemia. Nasal fiberscopy revealed septal perforation and multiple ulcers on her pharynx. The biopsy specimen from the pharyngeal ulcers showed a polymorphous cellular infiltrate without necrotizing vasculitis or granuloma. However, there were no atypical lymphocytes that are typically seen in nasal NK/T lymphoma. By immunohistochemical analysis, the infiltrated lymphocytes were proved to be T cells and Epstein-Barr virus encoded RNA (EBER) was not detected. No pulmonary or renal lesions resembling Wegener's granulomatosis were found. Taken together, the nasal septal perforation was considered as nasal involvement of PG.     

A subepidermal blistering dermatosis associated with coexistent IgG and IgA anti-dermal basement membrane zone antibodies; demonstration of IgG antibodies reactive against a 200-kDa dermal antigen

We report a 66-year-old woman presenting with an annular erythematous and bullous eruption. Her clinical and histological findings were similar to those of linear IgA bullous dermatosis or dermatitis herpetiformis. Direct immunofluorescence revealed linear deposition of IgA, IgG and C3 along the basement membrane zone (BMZ). Indirect immunofluorescence detected IgG and IgA antibodies against the BMZ. Salt-split skin technique demonstrated that IgG antibodies bound exclusively to the dermal side, while IgA antibodies bound not only to the dermal side, but also to the epidermal side with relatively weak intensity. On immunoblot analysis, the patient's IgG antibodies exclusively reacted with a band of 200-kDa, while the antigenic target of IgA antibodies was not identified. The present case is thought to be a unique bullous dermatosis mediated by both the IgG antibodies to a novel 200-kDa antigen and IgA antibodies against undetermined antigens.     

Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres

Summary Acquired cutis laxa (ACL) is an uncommon elastolytic disorder of unknown aetiology. In rare instances. ACL has been reported in association with autoimmune diseases and dermal deposit of immunoglobulins, suggesting that destruction of elastic tissue may be immunologically mediated. We report a 35-year-old man with generalized acquired cutis laxa (GACL) associated with a persistent papular erythematous eruption that histopathologically showed some resemblance to dermatitis herpetiformis. A marked reduction and degeneration of dermal elastic fibres was noted in biopsies from loose-hanging skin. Direct immunofluorescence from non-inflammatory loose skin revealed granular immunoglobulin A (IgA) deposits at the basement membrane zone and fibrillar IgA deposits in the dermal papillae. IgA deposits were also observed on the elastic fibres of the reticular dermis. Electron microscopy of skin from the submammary fold revealed fragmented elastic fibres, partial absence of peripheral microfibrils and abundant neutrophils, some of which were degranulated and adjacent to elastic fibres. Immunoelectron microscopy of an erythematous papule revealed IgA deposits around dermal elastic fibres. Antigliadin, antireticulin and antiendomysium antibodies were present. Jejunal biopsies showed a gluten-sensitive enteropathy. A possible IgA-mediated immune mechanism for the development of GACL in our patient is suggested.     

Skin changes caused by d-penicillamine treatment of arthritis

The clinical, histological and immunopathological details of three cases with a d -penicillamine-induced eruption are presented. The skin changes included (1) pemphigus erythematosus, (2) pemphigus foliaceus, (3) a bizarre localized pruritic papular eruption, the immunopathology of which was characteristic of lupus erythematosus and (4) fragility due to loss of dermal collagen. Circulating IgA was abnormally low in two cases and circulating immune complexes were demonstrated in the third case.     

POLYMORPHIC TYPE OF XANTHOMATOSIS IN ASSOCIATION WITH IgA MYELOMA

Clinical and immunochemical findings were reported from a 36-year-old woman with multiple xanthomas of various clinical types (plane xanthoma, tubero-tendinous, papulo-eruptive and follicular xanthomas), multiple myeloma (IgA, type L), and hyperlipemia with markedly elevated levels of plasma cholesterol and triglycerides. A bone marrow specimen showed foam cells and atypical plasma cell proliferation. Lipoprotein-IgA complexes were thought to exist in the serum of this patient on gel filtration and micro-ouchterlony test. Cutaneous xanthomas associated with multiple myeloma are plane xanthomas in most of the reported cases. Combination of several different types of xanthomas has been reported in only three cases, all of which were associated with IgA myeloma.     

A CASE OF MULTIPLE MYELOMA PRESENTING AS A BULLOUS DERMATOSIS

Multiple myeloma is a malignant plasma cell proliferative disorder that produces a monoclonal immunoglobulin protein. The skin involvement and the development of bullous disease are rarely seen features in multiple myeloma. We present a 55-year-old man with a longstanding, large, tense bullous eruption and hypertrophic scars over his body accompanied recently with weight loss and fatique. He had no response to the previous treatments, which included oral glucocorticoids and dapsone. Histologic examination of the lesions revealed subepidermal bullae, while no immunoflourescence staining was observed. In a further detailed labarotory examination, multiple myeloma was detected. After the treatment of multiple myeloma with chemotherapy, the lesions regressed. Patients with longstanding, recurrent, unusual bullous eruption should be investigated for the development of multiple myeloma.     

Acquired immunobullous disease: a cutaneous manifestation of IgM macroglobulinaemia

Summary Waldenstrom's macroglobulinaemia has been associated with a variety of cutaneous manifestations. We report a patient with an acquired bullous disorder associated with skin fragility and IgM kappa paraprotein. Immunofluorescence studies demonstrated bright linear deposition of IgM along the basement membrane zone (BMZ), around dermal blood vessels and on arrector pili muscles. Weak keratinocyte cell surface staining with IgM was also noted. There was no deposition of complement or other immunogiobulins. Indirect immunotluorescent studies revealed a circulating IgM anti-BMZ antibody (titre 1/200), which bound to both the roof and the floor of a 1 mol/l NaCI split skin substrate. Immunoblotting analysis ofthe patient's serum, with both epidermal and dermal extracts, was negative. Treatment with a combination of prednisolone and azathioprine was successful. We suggest that this IgM kappa paraprotein has a low affinity for an undefined epitope within the lamina lucida, which has produced a subepidermal bullous disorder associated with skin fragility.     

Multiple cutaneous plasmacytomas observed in IgD myeloma

A 79-year-old Japanese male patient with multiple cutaneous plasmacytomas in IgD-lambda myeloma is described. Initially, a very small amount of IgM paraprotein could be detected. This case was very aggressive clinically with prominent cutaneous involvement.     

Drug-induced linear IgA disease with antibodies to collagen VII

Linear IgA disease (LAD) is characterized by circulating and tissue-bound IgA antibodies against heterogeneous antigens in the cutaneous basement membrane zone. In most cases the cause is unknown, but a minority of cases has been drug induced. We report a 76-year-old man who developed an acute blistering eruption following high-dose penicillin treatment for pneumococcal septicaemia. Indirect immunofluorescence demonstrated dermal binding IgA antibodies, and Western blotting of serum showed reactivity with a 250 kDa dermal antigen corresponding to collagen VII of anchoring fibrils. Indirect immunoelectron microscopy showed antibody labelling in the lamina densa and sublamina densa zone. This is one of the few cases of drug-induced LAD in which the target antigen profile has been characterized, and the first in which the antigen has been shown to correspond to collagen VII.     

Plane xanthomata associated with multiple myeloma and hyperlipoproteinaemia

A case of plane xanthomatosis associated with multiple myeloma and hyperlipoproteinaemia in a 62-year-old woman is reported. The patient had IgG type lambda paraproteinaemia and type II A hyperlipoproteinaemia. The IgG paraprotein showed binding activity against high-density lipoprotein. It could not be demonstrated that these paraprotein-lipoprotein complexes were responsible for the hyperlipidaemia. Microchemical analysis of pathological skin demonstrated a high content of triglycerides, similar to that in eruptive xanthomata. No correlation was found between the lipid composition of the xanthomatous skin and the serum lipid composition. The results obtained with an in vitro culture method showed that the paraprotein present in the patient's serum was synthesized in the bone marrow but not in the normal or pathological skin.