Dominique C. Pichard

Primary immunodeficiency update: Part II. Syndromes associated with mucocutaneous candidiasis and noninfectious cutaneous manifestations

Several primary immunodeficiencies (PIDs) have recently been described that confer an elevated risk of fungal infections and noninfectious cutaneous manifestations. In addition, immunologic advances have provided new insights into our understanding of the pathophysiology of fungal infections in established PIDs. We reviewed PIDs that present with an eczematous dermatitis in part I. In part II of this continuing medical education article we discuss updates on PIDs associated with fungal infections, their biologic basis in PIDs, and noninfectious cutaneous manifestations.

Sorafenib-Induced Eruption Mimicking Erythema Multiforme

Additional Contributions: We are indebted to our consultant pathologist, Nicholas Francis, FRCPath, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, England; our consultant urologist, Michael Dinneen, MD, FRCSI, Chelsea and Westminster Hospital, London, England; and our consultant dermatopathologist, Florence Derodie, FRCPath, Royal Free Hospital, London, England. We are also grateful to our colleagues at various health care centers for bringing these patients to our attention and providing knowledge and expertise in the individual cases. These persons were not compensated for their contributions.

Diagnosis, Staging, and Treatment of Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) remains the primary cause of non–relapse-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), and the incidence of cGVHD continues to rise [1]. Evolving transplantation practices, including the use of mobilized peripheral stem cells, transplantation of older recipients, and more frequent use of mismatched transplants, may explain the occurrence of this vexing problem.

Beyond the triad: Inheritance, mucocutaneous phenotype, and mortality in a cohort of patients with dyskeratosis congenita

Age, y Median 23 32 Range 1-69 1-46 Age group, y 0-9 (n = 14) 14 (23) 6 (26) 10-19 (n = 14) 14 (23) 10 (43) 20-29 (n = 14) 14 (23) 5 (22) 30-39 (n = 7) 7 (12) 1 (4) 40-49 (n = 6) 6 (10) 1 (4)

Predictors for Permanent Discontinuation of Systemic Immunosuppression in Severely Affected Chronic Graft-Versus-Host Disease Patients

50 (n = 6) 6 (10) 0 DC gene TINF2 14 (23) — RTEL1 12 (20) 6 (26) DKC1 11 (18) 11 (48) TERT 10 (17) 1 (4) TERC 8 (13) — PARN 3 (5) 3 (13) ACD 1 (2) 1 (4) WRAP53 1 (2) 1 (4) CTC1 0 0 NHP2 0 0 NOP10 0 0 Sex Male 44 (73) 20 (87) Female 16 (27) 3 (13) No. of triad features 0/3 6 (10) 0 1/3 17 (28) 6 (26) 2/3 15 (25) 6 (26) 3/3 22 (37) 11 (48) No. of total features 0-2 23 (38) 7 (30) 3-5 21 (35) 7 (30) 6-9 16 (27) 9 (39)

Medallion-Like Dermal Dendrocytic Hamartoma, Dermatofibrosarcoma Protuberans, and Adenosine Deaminase-Deficient Severe Combined Immunodeficiency.

Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n = 54) or severe (n = 170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235). Patients received a median of 4 prior systemic therapy regimens and were seen at the NIH for a single time-point visit and were then monitored for survival and ability to discontinue cGVHD systemic therapy. With a median follow-up of 71.1 months, the cumulative incidence of systemic therapy discontinuation was 9.5% (95% confidence interval, 6.0% to 13.9%) at 2 years and 27.7% (95% confidence interval, 20.9% to 34.8%) by 5 years after the initial visit. Factors associated with a higher incidence of immunosuppression discontinuation included lower NIH global severity (P = .019) and lung (P = .030) scores and less extensive deep sclerosis (<37% body surface area, P = .024). Lower patient- and clinician-reported 0 to 10 severity NIH scores and noncyclosporine prophylaxis regimens were also associated with higher incidence of immunosuppression discontinuation (P <.05). In conclusion, we found low success rates for immune suppression discontinuation in previously treated patients who were severely affected with cGVHD. NIH scoring and clinical measures provide new standardized disease-specific tools to predict discontinuation of systemic therapy.

Early-onset stroke, polyarteritis nodosa (PAN), and livedo racemosa

To the Editor: We read with interest the report by Mutgi et al (1) regarding a 9-year-old girl with a CD34 dermal plaque consistent with a medallion-like dermal dendrocytic hamartoma (MDDH). The authors provided a summary of the limited reports in the literature of other MDDHs, noting that CD34 staining alone cannot differentiate between MDDH, a benign self-limited tumor, and dermatofibrosarcoma protuberans (DFSP), a low-grade sarcoma. Although the child with MDDH that Mutgi et al presented did not have a history of immunodeficiency, we would like to alert pediatric dermatologists to a high risk of DFSP tumors resembling MDDHs in children with adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID). At the National Institutes of Health, we have evaluated 15 children with ADA-SCID with one or more DFSP tumors. These tumors typically present as small (3– 6 mm), atrophic, hyperpigmented, indurated plaques. In several patients, multiple lesions have been detected (as many as 18 in an individual patient) (2). Although all individuals with ADA-SCID with DFSP tumors have molecular or cytogenetic confirmation of collagen type I alpha 1 gene platelet-derived growth factor B-chain gene (COL1A1-PDGFB) fusion, ADA-SCID-associated DFSPs are relatively hypocellular and do not possess the classic storiform pattern that would facilitate histologic differentiation of DFSP from MDDH (Fig. 1). As Kutzner et al (3) note in their comparison study ofMDDH and plaquelike DFSP, both types of tumors present as small, brown, atrophic or indurated plaques in children, and both tend to occur on the neck, trunk, and extremities. A similar distribution pattern of DFSPs has been detected in our ADA-SCID population. The natural history and optimal management of atrophic plaque-like DFSP in children with ADASCID is still uncertain, as is the pathophysiologic basis for susceptibility to multiple skin sarcomas in this immunodeficiency. Regardless, careful skin examination is critical when encountering this rare disease, and a low threshold for skin biopsy is needed. The detection of a CD34 spindle cell infiltrate in individuals with ADA-SCID should prompt testing for the COL1A1-PDGFB fusion product to confirm DFSP, even in the absence of classic storiform histology.

Primary immunodeficiency update: Part I. Syndromes associated with eczematous dermatitis

KEY TEACHING POINTS.