Richard I. Crawford

Cutaneous manifestations of chronic granulomatous disease. A report of four cases and review of the literature.

BACKGROUND Chronic granulomatous disease represents a group of genetic disorders in which impaired intracellular microbial killing by phagocytes leads to recurrent bacterial and fungal infections and granuloma formation. Cutaneous disease occurs in 60% to 70% of cases. The characteristic histologic finding of pigmented lipid macrophages in visceral granulomas has not been described previously in the skin. OBJECTIVE Our purpose was to review our experience of skin disorders in chronic granulomatous disease. METHODS We studied the clinical and histologic findings in four patients with chronic granulomatous disease and unusual skin lesions. We reviewed the skin disorders seen in five additional patients with chronic granulomatous disease referred to the pediatric dermatology clinic. The literature was reviewed for previously reported cutaneous manifestations of chronic granulomatous disease. RESULTS A teenage boy with chronic granulomatous colitis had nonulcerating cutaneous granulomas from which no organisms were isolated. Histologic examination of both skin and bowel revealed the characteristic golden-yellow granular pigment in macrophages. A second boy had cutaneous aspergillosis involving the left foot; histologic examination revealed macrophages containing yellow-brown pigment at the periphery of the granulomatous inflammation. Two children had vesicular skin lesions. These lesions were recurrent in one boy for several years. In the second child they were associated with fatal intracranial and pulmonary infection. Histologic examination in both cases revealed a subcorneal polymorphonuclear infiltrate and perivascular macrophages containing yellow-brown pigment. Cultures were either negative or revealed organisms that are normally nonpathogenic skin commensals, such as coagulase-negative staphylococci. CONCLUSION The cutaneous manifestations of chronic granulomatous disease encompass a variety of infections and inflammatory lesions. Diagnostic and therapeutic problems may arise because of difficulty in isolating a causative organism. The characteristic pigmented macrophages of visceral granulomas can also be found in skin lesions.

A Review of Adverse Cutaneous Drug Reactions Resulting from the Use of Interferon and Ribavirin

Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.

Actinic Granuloma is a Unique and Distinct Entity: A Comparative Study With Granuloma Annulare

Since the initial description of actinic granuloma (AG), debate has continued over whether it should be considered a specific condition or simply granuloma annulare (GA) located in sun-exposed areas of skin. We conducted a case-control study to clarify this issue. Twenty cases given the diagnosis of AG between 1991 and 2001 were retrieved from our archives. We applied the following inclusion criteria: extensive loss of elastic tissue in or at the side of the granuloma, and elastophagocytosis. Sixteen cases of GA that involved sun-exposed and non-sun-exposed sites, 8 cases from each group, were randomly selected as controls. Histologic parameters were quantitated on hematoxylin-eosin, Verhoeff van Gieson, and Alcian blue stains for each case. Results were statistically analyzed by SPSS program version 9. Fourteen cases of AG met our inclusion criteria. Presence of mucin, occurrence of multinucleated giant cells, and the type of granulomata were of high statistical significance (p < 0.01) in distinguishing the two entities. We also found that the location of the granulomata in these conditions is different and of statistical significance (p < 0.05). Based on histomorphology, we believe that AG should be considered a separate, independent condition and should be distinguished from GA even in sun-exposed areas of skin.

Calciphylaxis in the current era: emerging ‘ironic’ features?

BACKGROUND Calcific uraemic arteriolopathy (CUA), previously known as calciphylaxis, is a condition of microvascular calcification and thrombosis with resultant tissue necrosis. Due to the rarity of this disease, our understanding of its pathogenesis remains speculative. Iron has emerged as a potential pathogenic contributor to the development of CUA, but investigation into this link is lacking. The purpose of our study was to explore the clinical characteristics of patients diagnosed with CUA at our institution to allow for comparison to available literature. In addition, we wanted to pursue the possibility of iron being a pathogenic contributor to CUA development. We hypothesized that iron would have to be present in areas of microvascular calcification in order to play a contributing pathogenic role and, therefore, wished to establish whether iron deposition was present within available diagnostic CUA skin biopsy specimens. METHODS This study included all patients diagnosed with CUA at our institution between 1997 and 2009 whose tissue was available for further analysis. All available diagnostic skin biopsy specimens were reviewed and further analysed by a dermatopathologist. As the goal was to explore the potential pathogenic role of iron, staining for iron deposition within biopsy specimens was undertaken. All available medical and biochemical information about patients was also collated for analytic purposes and related to the biopsy specimen findings. RESULTS Tissue blocks from 12 patients diagnosed with CUA at our institution were available for further analysis. In this CUA cohort, the average age at diagnosis was 61 years (range, 36-83 years), with six (50%) patients being female. Of these patients, 8 (67%) had diabetes, 8 (67%) had coronary artery disease and 10 (83%) had dyslipidaemia. At the time of diagnosis, eight (67%) were on peritoneal dialysis, two (17%) on haemodialysis and two (17%) were pre-dialysis. Our patients had short dialysis vintage times prior to diagnosis (average, 2.1 years). Iron deposition was detected in areas of microvascular calcification in all diagnostic specimens and was absent in unaffected microvasculature within the same biopsy specimens. CONCLUSIONS The findings of iron deposition in affected microvasculature lend support to the potential role of iron in the complex pathophysiologic cascade of CUA. The implications for iron therapy in high-risk patients and the possible rationale for the use of sodium thiosulphate, a metal chelator, in the treatment of CUA are explored.

A pruritic linear urticarial rash, fever, and systemic inflammatory disease in five adolescents: Adult-onset Still disease or systemic juvenile idiopathic arthritis sine arthritis?

Abstract:  The characteristic rash of systemic juvenile idiopathic arthritis is a transient erythematous eruption associated with a quotidian spiking fever. Usually asymptomatic, it can be pruritic, with dermatographism at sites of scratching or pressure. An illness similar to this entity in adults is designated adult‐onset Still disease. The relationship between the pediatric and adult disease is uncertain and differences in case definition have evolved. Specifically, a sustained arthritis for at least 6 weeks is required for a diagnosis of systemic juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are accepted criteria in adult‐onset Still disease. We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. Intense pruritus and linear erythematous lesions flared with a spiking fever, usually in the late afternoon and evening. Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two children had splinter hemorrhages of the nail beds and one girl developed a fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. The course of the disease was variable. One patient, diagnosed with macrophage activation syndrome, recovered on oral naproxen. Two patients responded to systemic corticosteroid therapy. One girl developed status epilepticus and died from aspiration and asphyxia. A boy with severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he had recurrent episodes of rash and fever into adult life. These children did not fulfill the case definition of systemic juvenile idiopathic arthritis because they lacked a persistent arthritis. Adolescent and adult patients with the same clinical and laboratory findings are described under the rubric of adult‐onset Still disease. Recognition of the distinctive urticarial skin eruption and spiking fever is important in the diagnosis of a disease with severe morbidity and potentially life‐threatening complications.

Benign lichenoid keratoses with histologic features of mycosis fungoides: clinicopathologic description of a clinically significant histologic pattern

Background: Benign lichenoid keratosis (BLK) is a well‐known clinicopathologic entity and several histopathologic patterns havebeen described. Features mimicking mycosis fungoides (MF) in clinically typical BLKs have not yet been emphasized. The aim of this study was to confirm the occurrence of an MF‐like pattern of BLK.

Medical management of eating disorders: a practical handbook for health care professionals

Part I. The Medical Perspective: 1. Definitions and epidemiology 2. The behavioural disorders 3. History, examination and investigations 4. Medical manifestations by system 5. The clinicians response to common physical complaints Part II. Treatment: 6. Principles of treatment 7. Medical and nutritional therapy Part III. Special Issues: 8. Specific patient populations 9. Prepubertal child and the younger adolescent Part IV. The Psychiatric and Psychological Perspective: 10. Physical disease and mental illness: pathology and psychopathology 11. Psychopathology and the mental status examination 12. Psychopathology and phenomenology 13. Specific psychological therapies Part V. Areas of Special Interest: 14. The role of the general practitioner 15. Nursing patients with anorexia nervosa 16. The role of the dietitian 17. Information for family and friends Bibliography Index.

Transient erythroporphyria of infancy

We describe a neonate with hemolytic disease of the newborn in whom a photosensitivity eruption developed during phototherapy for treatment of hyperbilirubinemia. Free erythrocyte protoporphyrin and zinc protoporphyrin levels were markedly elevated during the neonatal period. Porphyrin levels were normal at 19 weeks of age. The infant had residual skin atrophy and showed clinical and radiologic evidence of kernicterus. The pathogenesis of transient porphyrinemia associated with hemolytic disease of the newborn is unclear.

Mitotic granuloma annulare: a clinicopathologic study of 20 cases

The finding of mitotic figures in granuloma annulare (GA) has not been emphasized in the literature. We describe 20 cases of a cellular, mitotically active variant of GA; we defined this group as cases having ≥ 1 mitosis per 10 hpf. Clinically, the lesions could not be distinguished from typical, localized GA: there were 9 males and 11 females with a mean patient age of 49±15 years (mean±SD), compared to 45±20 years in a randomly selected control group of 60 patients with GA, and no unusual sites of predilection were noted. Histologically, a classic, palisading granuloma pattern predominated (18/20 cases). Lesions were located in the mid‐dermis and tended to be more cellular than typical GA. The histiocytes comprising the lesion often had enlarged nuclei and prominent nucleoli. The number of mitoses per 10 hpf was 3.0±1.5 (range 1.0–7.2), control group 0.3±0.5; occasional atypical mitotic figures were observed. The proliferative nature of these lesions was confirmed using MIB‐1 staining; the percentage of MIB‐1 positive cells ranged from 5%–29% (mean 15±6%). Mitotic GA must be distinguished histologically from neoplastic processes, in particular epithelioid sarcoma. We conclude that histiocytes in clinically typical GA can exhibit an increased mitotic rate. Recognition of this variant is important in order to avoid overdiagnosis of a malignant condition.

A quantitative study of epidermal Langerhans cells in cutaneous leishmaniasis caused by Leishmania tropica

Objective  The purpose of this study was to characterize the number and distribution of epidermal Langerhans cells in different clinical forms of dry‐type cutaneous leishmaniasis (CL).