Hypereosinophilic syndrome in an atopic patient

Hypereosinophilic syndrome (HES) is a rare, heterogeneous group of systemic diseases characterized by sustained overproduction of eosinophils leading to variable end‐organ damage. The skin is affected in 45–60% of patients and may be of diagnostic and prognostic value. In 1975, three criteria were suggested for the diagnosis of HES: (i) blood eosinophilia of > 1.5 × 10⁹/L present for > 6 months, (ii) no apparent cause for the hypereosinophilia, and (iii) signs of end‐organ dysfunction. We present a patient with hypereosinophilia in whom a delay in diagnosing HES occurred, partly due to his atopic constitution. However, atopy is not associated with such high or longstanding eosinophilia.     

Hypereosinophilic syndrome: cutaneous involvement as the sole manifestation

Hypereosinophilic syndrome (HES) encompasses a group of leukoproliferative disorders with variable involvement of the internal organs. More than half of all patients have cutaneous involvement. In a minority of the reported cases, skin involvement has been the only manifestation of HES . We report one such rare case of HES, with cutaneous involvement as the sole manifestation.     

A case of hypereosinophilic syndrome

A 22-year-old man developed papules on his legs in November of 2001, which then spread to cover almost his entire body. He was treated with a topical steroid and PUVA therapy at another hospital. The symptoms showed no improvement, and, in February of 2002, he came to our hospital. Examination revealed hypereosinophilia, and, because he had symptoms of organ involvement by the heart, lung, and inguinal lymph nodes as well as the skin, we diagnosed him with idiopathic hypereosinophilic syndrome (HES). The patient was treated with oral prednisolone at a dose of 60 mg/day, and his cutaneous lesions and other organ symptoms improved.     

Infectious urticaria with purpura: a mild subtype of urticarial vasculitis?

Urticaria is characterized by transient wheals. We report here five cases with long-lasting urticarial lesions persisting for more than 24 hours. Each lesion left purpura after fading. There was no systemic involvement. C-reactive protein and serum levels of complement were elevated or normal. Histologically, marked infiltration by eosinophils and neutrophils with karyorrhexis in the perivascular and intercollagenous spaces was observed, but there was no evidence of vasculitis (venulitis). Skin symptoms were resistant to systemic corticosteroids. In contrast, treatment of underlying bacterial infections resulted in marked improvement of skin lesions. E-selectin, VCAM-1 and ICAM-1 were expressed on endothelial cells. Marked deposition of C3a, C5a, neutrophil elastase and major basic protein in the dermis was observed. These urticarial lesions provoked by bacterial infections seem to lie on the continuum between urticaria and urticarial vasculitis.     

Persistent urticaria--urticarial reaction caused by late phase reaction?

In ordinary urticaria, individual lesions disappear within 24 hours. We encountered 3 patients who showed urticarial reactions lasting more than 24 hours. In all patients, skin biopsy revealed interstitial dermal edema and a perivascular infiltration predominated by eosinophils, without immunoglobulins or complement deposition, or endothelial fibrinoid degeneration. Their eosinophil counts and serum complement levels were within normal range. No proteinurea or joint pain was observed. They could not be controlled by any medications except for glucocorticoid. These findings indicate our cases are not ordinary urticaria, urticarial reaction accompanied by eosinophilia, urticarial vasculitis or delayed pressure urticaria. We recognize such urticarial reaction as a different clinical entity from the usual urticaria, and we speculate that this condition is caused by late phase reaction because of the clinical course and eosinophil infiltrations.     

Osteosarcoma of the skin

Background Osteosarcoma is a common malignancy, although skin metastasis is rare. We sought to review the incidence, epidemiology, risk factors, and prognosis of osteosarcoma with skin involvement. Methods We conducted a retrospective chart review that covered 30 years and involved clinic patients younger than 18 years who had cutaneous metastases of osteosarcoma. The main outcome measure was histologic documentation of both primary tumor and metastatic lesion in the skin. Results Two patients were found to have osteosarcoma with skin involvement. No unifying factors were identified. Conclusions Although osteosarcoma is a common malignancy with frequent metastases, involvement of the skin is rare. Further studies to identify risk factors and subsequent prognosis are necessary. Nevertheless, unidentifiable skin lesions in a patient with a history of osteosarcoma should be investigated to rule out tumor metastasis, regardless of cancer status.     

Dress syndrome with sepsis, acute respiratory distress syndrome and pneumomediastinum

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, and is characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause DRESS syndrome. We report a case of a 10-year-old girl who developed clinical manifestations of fever, rash, lymphadenopathy, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis) after taking phenobarbital for seizures, with subsequent development of sepsis, acute respiratory distress syndrome (ARDS) and spontaneous air leak syndrome (pnemothorax and pneumomediastinum). She was put on steroids and various antibiotics and was ventilated, but ultimately succumbed to sepsis and pulmonary complications.     

Urticarial vasculitis with blister formation: bullous (vesicular) urticarial vasculitis

A 37-year-old woman developed blistering on urticarial erythematous lesions. She had multiple joint pain, subfever, alopecia, high antinuclear factor, and hypocomplementemia. She was diagnosed as having SLE. Her SLE symptoms responded well to steroid therapy, whereas her urticarial lesions responded to DDS but not to steroid. Histology of her skin lesions resembled that of dermatitis herpetiformis. We suggested the term “bullous (Vesicular) urticarial vasculitis” to distinguish such a case with peculiar manifestations in urticarial vasculitis.     

Cutaneous Waldenstrom macroglobulinemia in transformation

Waldenstrom macroglobulinemia is a low-grade B-cell lymphoproliferative disorder of the elderly with characteristic monoclonal IgM-producing neoplastic infiltrates of the bone marrow, lymph node, and spleen. Cutaneous manifestations are usually nonspecific such as purpura, ulcers, and urticarial lesions. These lesions are caused by hyperviscosity of the blood, immune complex-mediated vascular damage, paraprotein deposition, and amyloid deposition. Specific skin lesions occur rarely and generally consist of translucent, flesh-colored papules composed of monoclonal IgM deposits. Rarely, there may be violaceous lesions composed of low-grade lymphoplasmacytic infiltrates characteristic of Waldenstrom macroglobulinemia. Both cutaneous manifestations of the disease, as well as disease transformation to high-grade, large cell lymphoma are rare. We report two very unusual cases of Waldenstrom macroglobulinemia with documented skin disease that demonstrated transformation to high-grade lymphoma. Both patients were elderly men with long-standing Waldenstrom macroglobulinemia involving the bone marrow, who subsequently developed skin involvement by the disease. Waldenstrom macroglobulinemia can rarely manifest as cutaneous disease, sometimes as a high-grade transformation of low-grade Waldenstrom macroglobulinemia elsewhere. Distinction of cases of transformed Waldenstrom macroglobulinemia from de novo cutaneous large cell lymphoma may be important, because the two entities are likely biologically different.     

Annular urticarial lesions

Annular urticarial configurations are often associated with acute and chronic urticaria. Such lesions may be short-lived, migratory, transient, pruritic, and resolving with no residual evidence, making the diagnosis of urticaria an obvious one. Annular urticarial lesions can be the presenting signs of various cutaneous and systemic diseases. The differentiation of urticarial lesions may be made by considering the duration of an individual lesion longer than 24 hours, with burning and pain sensation in the lesions or lack of pruritus; skin marks such as postinflammatory pigmentation or purpura after resolution of the lesions; associated scaling or vehiculation in the lesions; systemic symptoms such as arthralgia, fever or fatigue; and several abnormal laboratory findings. The main differential diagnoses of annular urticarial lesions include urticarial vasculitis, autoinflammatory syndromes, hypersensitivity reactions, and connective tissue diseases.     

Lymphocytic variant of hypereosinophilic syndrome

Hypereosinophilia may be associated with any of several underlying diseases. Atopy or allergic drug reactions are the most common causes, but infections with bacteria and parasites should also be considered in the differential diagnosis. When thorough evaluation of a patient with chronic hypereosinophilia fails to reveal an underlying disease, the diagnosis of idiopathic hypereosinophilic syndrome (HES) should be considered. We report a patient with unexplained persistent hypereosinophilia associated with a chronic pruritic rash and an underlying diagnosis of HES (lymphocytic variant).     

Benign hypersensitivity reactions to smallpox vaccine

BACKGROUND: With the reinstitution of smallpox vaccinations, physicians are seeing significant numbers of adverse events for the first time since the 1980s. The most common adverse events seen in our large military population are benign. We observed a clinically and histopathologically distinct reaction pattern that has not been fully characterized previously. METHODS: All smallpox-vaccinated patients at Fort Hood, Texas with adverse cutaneous reactions were referred to the dermatology clinic at Darnall Army Community Hospital. Patients were evaluated by a staff dermatologist who performed a skin biopsy and took clinical photographs. If the patients had intact vesicles or pustules, direct fluorescent antibody testing, viral and bacterial cultures, and polymerase chain reaction (PCR) assays were also performed. RESULTS: Three hypersensitivity reaction patterns were seen: exanthematous, erythema multiforme-like (EM-like), and urticarial. The patterns had distinct clinical and histopathologic findings. Of the 11,058 vaccinees, six had the exanthematous reaction pattern, two had the urticarial reaction pattern, and one had the EM-like pattern. CONCLUSIONS: We describe a new exanthematous type of hypersensitivity reaction to the smallpox vaccine. Hypersensitivity reactions occur at a rate higher than previously reported. In a carefully screened military population, these three hypersensitivity reactions are much more common than life-threatening or serious reactions. Although the reactions have distinct clinical and pathologic features, they are all characterized by mild or absent systemic symptoms and a benign outcome.     

Increased fibroblast elastase activity in acquired cutis laxa.

BACKGROUND: Acquired cutis laxa is a rare disease characterized by sagging skin, premature wrinkling and reduced skin elasticity. OBSERVATION: We report a 21-year-old woman, who presented with acquired cutis laxa on the face and the ear lobes. Urticarial papules had preceded for 6 years. There was no systemic involvement. Skin specimens were obtained from lax skin and urticarial papules, and from healthy controls. Histology showed only few perivascular lymphocytes in lax ear skin and a dense inflammatory infiltrate in urticarial skin. In both biopsies elastic fibres were decreased as demonstrated by computerized morphometric analyses. Elastase activities of fibroblasts in culture were evaluated. There was a 2- to 3-fold increase in elastase activity in urticarial skin fibroblasts, contrasting with a normal elastase activity in lax ear skin. CONCLUSION: Our findings suggest that the inflammatory cells could play a significant role in the destruction of elastic fibres.     

Urticarial vasculitis in an infant

Urticarial vasculitis (UV), a subtype of leukocytoclastic vasculitis, is a small vessel necrotizing vasculitis characterized by urticarial lesions and decreased serum complement. Primarily a disease of adult women, this immune complex disorder is seldom reported in children. Pathologic examination of skin lesions in patients with UV reveals leukocytoclastic vasculitis. UV is a frequent finding, particularly involving early components of the classical complement cascade C1q and C2 to C4. We report a 9-month-old male infant who presented with chronic urticaria of 7 months' duration that was unresponsive to conventional therapies for urticaria. His lesions appeared as erythematous wheals followed by the development of purpuric papules and resolving with ecchymoses and postinflammatory hyperpigmentation. Laboratory studies and skin biopsy results were consistent with UV.     

Hypereosinophilic syndrome with various skin lesions and juvenile temporal arteritis

Hypereosinophilic syndrome (HES) is a multisystem disease with a high mortality rate. It is characterized by peripheral blood eosinophilia and eosinophilic infiltration of the skin and many other organs. The commonest cutaneous features include erythematous pruritic maculopapules and nodules, angio-oedema or urticarial plaques. However, some case reports have indicated that eosinophilic cellulitis, cutaneous necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene may also occur as cutaneous features of HES. Juvenile temporal arteritis (JTA) of unknown cause is characterized by an asymptomatic nodule in the temporal artery area in young adults. Histologically, the lesion is characterized by a significant intimal thickening with moderate eosinophilic infiltrates, constriction or occlusion of the vascular lumen and absence of giant cells. We report a patient with HES presenting with eosinophilic cellulitis, Raynaud's phenomenon, digital gangrene and JTA. JTA may also be one of the features of HES.     

Extensive neurocristic hamartoma with skeletal muscle involvement

Neurocristic hamartomas (NCH) are rare pigmented skin lesions based in the deep subcutaneous tissues that may be either congenital or acquired. The clinical importance of these lesions is the potential for misdiagnosis and the development of malignant melanomas over a poorly described time course. Histological pleomorphism precludes meaningful random biopsies as a means of cancer surveillance. We present the case of an extensive NCH in a 67-year-old man, with a reported duration of greater than 50 years and no current clinical or histological indication of malignancy. Incisional biopsies of nodular areas showed bland-appearing pigmented cells that extended into subcutaneous adipose tissue and skeletal muscle. The specimens contained numerous clusters of differing configurations and cell types. Positron emission tomography (PET) scanning was used as an adjunct to physical examination in follow up. A PET-avid mass was detected but proved to be a banal nodular melanocytic proliferation within the NCH. In conclusion, NCH may be characterized by extensive deep tissue involvement in the absence of overt malignancy. The possible development of malignant melanoma in such lesions warrants close surveillance.     

Hypocomplementemic urticarial vasculitis in mixed connective tissue disease

Urticarial vasculitis is characterized clinically by urticaria-like skin lesions and histologically by leukocytoclastic vasculitis. It may be idiopathic or associated with various conditions such as infections, hematologic disorders, drugs, and connective tissue diseases, primarily systemic lupus erythematosus; an association with mixed connective tissue disease (MCTD) has rarely been reported. We present a case of hypocomplementemic urticarial vasculitis in a patient with MCTD that responded to hydroxychloroquine after a period of corticosteroid dependence.     

A retrospective analysis of 34 patients with cutaneous sarcoidosis assessed in a dermatology department

Background. Sarcoidosis is a multisystem granulomatous disease of unknown aetiology, which most often involves the lungs and lymphatic system. Cutaneous involvement is found in approximately 25% of cases of sarcoid. Most previous studies of cutaneous sarcoidosis have been drawn from populations with defined pulmonary disease, so may represent a population with more systemic involvement. Objective. We describe a cohort of patients with cutaneous sarcoid seen in a dermatology department. Methods. Case records were reviewed for patients with a histopathological diagnosis of noncaseating sarcoidal granuloma on skin biopsy, taken between 1996 and 2005. Results. In total, 34 patient records were analysed; 21 patients were found to have extracutaneous systemic sarcoid and 10 patients had sarcoid localized to the skin. Patients with lupus pernio and with ulcerated sarcoid lesions all had extracutaneous disease. No other cutaneous features, including the extent of cutaneous disease, were found to be predictive of systemic involvement. Conclusions. All patients presenting to a dermatology department with cutaneous sarcoidal granulomas require investigation for systemic sarcoid. Our data suggest that approximately 30% of patients seen in a dermatology clinic with cutaneous sarcoidal granulomas will have disease apparently limited to the skin.     

Skin rash and arthritis a simplified appraisal of less common associations

Skin and joint manifestations are part of the clinical spectrum of many disorders. Well‐known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low‐specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo‐papular, vesico‐bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non‐febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small‐vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information.     

Churg-strauss syndrome

Churg-Strauss syndrome (CSS) is a rare granulomatous necrotizing small vessel vasculitis characterized by the presence of asthma, sinusitis, and hypereosinophilia. The cause of this allergic angiitis and granulomatosis is unknown. Other common manifestations are pulmonary infiltrates, skin, gastrointestinal, and cardiovascular involvement. No data have been reported regarding the role of immune complexes or cell mediated mechanisms in this disease, although autoimmunity is evident with the presence hypergammaglobulinemia, increased levels of IgE and Antineutrophil cytoplasmic antibody (positive in 40%). We report the case of a 27-year-old lady presenting with painful swelling of predominantly lower limbs with extensive vesicles and ecchymotic patches and fever shortly after stopping systemic steroids taken for a prolonged duration (2002--2010). The aim of this case report is to point to the possibility of CSS in patients presenting with extensive skin lesions masquerading as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome (SJS/TENS).