Cholesterol embolization syndrome: cutaneous histopathological features and the variable onset of symptoms in patients with different risk factors

Cholesterol embolization syndrome (CES) may not only be due to direct dislodgement of cholesterol crystals from atherosclerotic plaques on the walls of arteries by surgery, angiogram or trauma, but may occur after anticoagulant and thrombolytic therapy. The latter two therapies both weaken the fibrin clot that stabilizes the atheromas in place; however, these two therapies commonly have different onsets of CES after their institution. We present three patients with different risk factors for CES who all presented with the pathognomonic triad of leg and/or foot pain, livedo reticularis and good peripheral pulses. In all three patients cholesterol emboli were demonstrated in cutaneous biopsy sections. In two patients there was associated renal involvement, which was fatal in one case. These cases illustrate that cutaneous biopsy may be diagnostic in patients with livedo reticularis, which progresses to necrosis and gangrene. In addition, they illustrate the problems and contradictions involved in treating patients with CES.     

Cholesterol crystal embolization: skin manifestation, gastrointestinal and central nervous symptom treated with corticosteroid

Cholesterol crystal embolization (CCE) is characterized by tissue ischemia secondary to occlusion of small arteries. It may occur spontaneously but more often follows radiological interventional procedures or vascular surgery. This systemic disease affects multiple organs, including skin, kidney, brain, eye, and gastrointestinal tract. We reported a Japanese male CCE patient with cutaneous manifestations of livedo reticularis, diarrhea, clouding of consciousness, and acute renal failure. Histopathological examination demonstrated multiple biconvex clefts in a vessel of the subcutis. Corticosteroid administration improved his consciousness, diarrhea and skin lesions. Awareness of the skin manifestations of CCE is essential for dermatologists to make an early diagnosis and prescribe appropriate treatment.     

Successful use of heparin and warfarin in the treatment of cholesterol crystal embolization

We report an 81-year-old male with cholesterol crystal embolization (CCE). He had been treated with warfarin for atrial fibrillation and an old cerebral infarction but had recurrence of cerebral infarction after warfarin was discontinued as treatment of CCE. Anticoagulation therapy by heparin in addition to warfarin was restarted, with the result that symptoms of cerebral ischemic damage did not recur and skin manifestations of CCE rapidly improved. These results suggest the possibility that heparin may be effective in the treatment of CCE, because CCE is not the result of pure embolization by cholesterol crystals but is a result of a combination with simultaneous thrombi.     

Multicentric Castleman disease with cutaneous manifestations: report of 2 cases and comparison with systemic plasmacytosis

We report 2 patients with multicentric Castleman disease. Both presented with multiple, indurated, hyperpigmented plaques, generalized lymphadenopathy and polyclonal hypergammaglobulinemia. Biopsy specimens showed infiltration of mature plasma cells and lymphocytes in the dermis and lymph nodes. Skin specimens were negative for human herpesvirus 8, latent nuclear antigen 1 and Epstein-Barr virus by in situ hybridization. PCR disclosed clonal T-cell receptor gene rearrangement in the bone marrow cells of 1 patient. We discuss the possible relationship between multicentric Castleman disease and systemic plasmacytosis as well as plasma cell proliferation.     

IgG4‐related disease with cutaneous manifestations treated with rituximab: Case report and literature review

Immunoglobulin type gamma 4 (Ig)G4‐related disease (IgG4‐RD) is a relatively recently described clinical entity characterised by elevated levels of serum IgG4 and tissue infiltration of IgG4+ plasma cells in various organ systems. Cutaneous involvement is rare but is becoming increasingly appreciated; typically presenting as erythematous papules and/or nodules that are commonly pruritic. We report a case of IgG4‐RD presenting with persistent pruritic papules and unilateral parotid swelling. His serum IgG4 level was elevated and a histological examination of his skin biopsies found a lymphoplasmacytic infiltration with an excess of IgG4+ non‐clonal plasma cells. The patient was intolerant of oral prednisolone, however complete resolution of the cutaneous lesions was achieved with the anti‐CD20 antibody, rituximab.     

Scleromyxoedema: treatment of cutaneous and systemic manifestations with high-dose intravenous immunoglobulin

Scleromyxoedema is a rare disease characterized by cutaneous sclerosis, mucin deposition and paraproteinaemia. Internal disease is common, particularly musculoskeletal, gastrointestinal and central nervous system involvement. We report a series of three consecutive patients with scleromyxoedema treated with high-dose intravenous immunoglobulin (hdIVIg). Each of the three patients had relatively low levels of a highly basic IgG-lambda paraprotein, and each has demonstrated a sustained response of both their cutaneous and extracutaneous disease to hdIVIg. As all patients had perioral skin involvement and microstomia, one measure of cutaneous improvement was the increase in intraincisor distance. Extracutaneous manifestations of scleromyxoedema that improved included ureteral stricture, vocal strength and dysphagia.     

Molecular diagnosis of cutaneous leishmaniasis and species identification: analysis of 122 biopsies with varied parasite index

Background: Cutaneous leishmaniasis is endemic in the Middle East and North Africa. Confirming the diagnosis histologically depends on amastigote identification, which varies significantly depending on the inoculum, strain type, host response and disease stage. Accurate histological diagnosis is mandatory for appropriate therapy. Methods: Skin biopsies from 122 patients from Lebanon, Syria and Saudi Arabia with clinical diagnosis of untreated leishmaniasis were reviewed and clinical data extracted. Cases were classified according to the modified Ridley's parasitic index. DNA was extracted from formalin‐fixed paraffin‐embedded blocks. Polymerase chain reaction (PCR) was performed using Leishmania‐specific ribosomal internal transcribed spacer 1 (ITS1‐PCR). Nested ITS1‐PCR was performed on cases negative for conventional ITS1‐PCR. ITS1‐PCR amplicons were digested with HaeIII for subsequent restriction fragment length polymorphism (RFLP) subspeciation. Results: Of 122 cases, 54 (44.3%) showed a parasitic index of 0–1+ (no unequivocal amastigotes). ITS1‐PCR (conventional and nested) was positive for all cases as compared with negative control tissue. RFLP identified Leishmania tropica in all cases. Patients with clinically suspected leishmaniasis, whose skin biopsies failed to detect amastigotes represented 44.3% of our cases. Conclusions: In this study, we describe a rapid and optimized protocol from DNA extraction to leishmaniasis subspeciation. ITS1‐PCR showed high sensitivity and specificity in confirming clinically suspected cases. Yehia L, Adib‐Houreih M, Raslan WF, Kibbi A‐G, Loya A, Firooz A, Satti M, El‐Sabban M, Khalifeh I. Molecular diagnosis of cutaneous leishmaniasis and species identification: analysis of 122 biopsies with varied parasite index.     

Sarcoidosis with cutaneous perineural granulomas and neurological manifestations: A potential mimicker of leprosy

Sarcoidosis is a granulomatous condition with diverse clinical presentations, including neurological findings. It was previously hypothesized that perineural sarcoidal granulomas in the skin may be an explanation of small-fiber neuropathy. Herein, we present a case of a 55 year old female with anesthetic cutaneous lesions mimicking leprosy clinically and histopathologically and discuss the importance of this differential diagnosis.     

Glycosylated proteins of stratum corneum, nail and hair in diabetes mellitus: correlation with cutaneous manifestations

Nonenzymatic glycosylation of protein may play some role in the development of diabetic complications. To study the association of nonenzymatically glycosylated protein in keratinized tissues with the prevalence of cutaneous manifestations frequently observed in diabetics, we measured furosine values of stratum corneum, nail and hair from 61 diabetics and assessed their cutaneous manifestations. The manifestation most frequently found in this study was 10 cases of pigmented pretibial patches. We did not detect significant correlations between the prevalence of any cutaneous manifestations and furosine values of any keratinized tissues. However, 11 of the 17 patients with yellow nail showed high nail furosine values. Our data suggest that nonenzymatically glycosylated protein levels in the keratinized tissues do not correlate with the prevalence of cutaneous manifestations in diabetics, but do not exclude a role in the formation of yellow nail.     

Erdheim-Chester disease presenting with cutaneous involvement: a case report and literature review

Erdheim-Chester disease (ECD) is a rare, systemic, non-familial histiocytic disorder, first described by Jakob Erdheim and William Chester in 1930. Most patients have multiple sites of involvement at presentation. The most common site of involvement is the long bones of the axial skeleton, which is seen almost universally, followed by the nervous system, heart, lungs, orbit and retroperitoneum, which are seen in up to 50% of cases. Cutaneous involvement is rarely a presenting symptom of ECD, with two reported cases in the English literature. The diagnosis of ECD is rarely made by skin biopsy because of the relative rarity of cutaneous involvement as a presenting feature, and also perhaps because of the difficulty in distinguishing the histopathological appearance from potential mimics. The importance of distinguishing ECD from other cutaneous disorders with similar pathology lies in the implications for both treatment and prognosis. ECD is an aggressive, often fatal disorder, with death from disease occurring in greater than 50% of patients.     

Case of primary localized cutaneous amyloidosis with protean clinical manifestations: lichen, poikiloderma-like, dyschromic and bullous variants

Primary localized cutaneous amyloidosis (PLCA) commonly presents as macular and lichen variants. We present a case of a 27-year-old Chinese woman with cutaneous features of the rarely reported poikiloderma-like, dyschromic and bullous forms of PLCA, and the commoner lichen variant. There were no syndromic associations or systemic involvement, and the various morphological subtypes occurred in isolation from one another. We review the clinical spectrum of PLCA, highlight its protean clinical manifestations in this patient, and discuss its postulated pathogenesis in relation to its histopathological features.     

Cronkhite–Canada syndrome: A rare disease presenting with dermatological and gastrointestinal manifestations

We present a case of Cronkhite–Canada syndrome, which is a rare disease classically characterised by hyperpigmentation, alopecia and onychodystrophy associated with clinical gastrointestinal symptoms and hamartomatous gastrointestinal polyps. Management primarily involves immunosuppression and nutritional support, which led to remission in this case. The recognition of cutaneous features may lead to early diagnosis and reduce morbidity and mortality.     

Rosai-Dorfman disease complicated by autoimmune haemolytic anaemia: case report and review of a multisystem disease with cutaneous infiltrates

We report a patient with sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) who presented with widespread nodal and extranodal involvement affecting the skin, orbits and nasal sinuses, complicated by the development of autoimmune haemolytic anaemia. The aetiology and pathogenesis of this multisystem disorder are unknown but are thought to represent a reactive histiocytic process to an infective agent rather than a neoplastic or other primary condition. Prognosis is generally good but clinical or laboratory evidence of immune dysfunction tends to predict a poorer outcome. We describe the clinical course of the patient and review the literature on this disease.     

Macular arteritis associated with concurrent HIV and hepatitis B infections: a case report and evidence for a disease spectrum association with cutaneous polyarteritis nodosa

We report the first case of macular arteritis in a 33‐year‐old Black, African female with concurrent human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Of particular interest in macular arteritis is the striking discordance between the clinical presentation and the histopathological findings, a fact that both dermatologists and dermatopathologists should be aware. Histopathologically, the case showed typical findings of macular arteritis with a perivascular, predominantly lymphocytic, infiltrate and intraluminal thrombosis. Both HIV and HBV have been reported as viral inducers of cutaneous polyarteritis nodosa (PAN). Their association with macular arteritis in this case supports existing evidence that macular arteritis and cutaneous PAN represent a single‐disease spectrum of vasculitides, with macular arteritis representing the chronic, lymphocytic and indolent stage, and cutaneous PAN the neutrophilic, acute stage with a risk for systemic progression. Lymphocytic thrombophilic arteritis (LTA), a third, uncommon disease would be in between macular arteritis and cutaneous PAN on a spectrum. Features of this case and other published cases provide strong evidence that there is a single, mild‐to‐severe disease spectrum of macular arteritis‐LTA‐cutaneous PAN.