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Background

This is a rare blistering disorder, usually affecting children, occurring after exposure to sunlight. There may be an association with Epstein-Barr virus infection. The blisters characteristically heal with scarring.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
INCIDENCE Rare
AGE RANGE-MEDIAN Usually childhood

 

DISEASE ASSOCIATIONS CHARACTERIZATION
LYMPHOMA  

Coexistence of hydroa vacciniforme and malignant lymphoma.

Oono T, Arata J, Masuda T, Ohtsuki Y.

Arch Dermatol 1986 Nov;122(11):1306-9 Abstract quote

Ten years after the onset of hydroa vacciniforme (HV), a 16-year-old boy developed edema and red induration of the face, ears, and dorsa of the hands.

Aggravation of cutaneous manifestations was associated with general malaise, headache, fever, lymphadenopathy, hepatosplenomegaly, and an increase of several serum enzymes. The vesicle was situated intraepidermally with thrombosis and hemorrhage underneath. This confirmed the diagnosis of HV. In addition, dense cell infiltrate was seen in deep dermis and subcutaneous tissue. Histologic and immunohistochemical studies of the dermal cell infiltrate and lymph node showed an infiltrate of helper T lymphocytes with an atypia and histiocytic cells (S100[-], alpha-subunit[+]).

Hence, we concluded HV and malignant lymphoma coexisted in this patient.

 

PATHOGENESIS CHARACTERIZATION
EPSTEIN-BARR VIRUS  

The association of latent Epstein-Barr virus infection with hydroa vacciniforme.

Iwatsuki K, Xu Z, Takata M, Iguchi M, Ohtsuka M, Akiba H, Mitsuhashi Y, Takenoshita H, Sugiuchi R, Tagami H, Kaneko F.

Fukushima Medical University School of Medicine, 1-Hikarigaoka, Fukushima 960-1295, USA.

Br J Dermatol 1999 Apr;140(4):715-21 Abstract quote

Patients with hydroa vacciniforme (HV)-like eruptions and malignant potential have been reported from Asia and Mexico, and those patients frequently had an associated latent Epstein-Barr virus (EBV) infection.

In order to elucidate the association of latent EBV infection with HV, we studied six children with typical manifestations of HV by detection of EBV genes and EBV-related RNAs in biopsy specimens from cutaneous lesions.

Cutaneous lesions of all six children with typical HV contained EBV-encoded small nuclear RNA (EBER)+ cells in 3-10% of the dermal infiltrates, whereas no Bam HI-H, l-fragment (BHLF) mRNA, or transcripts encoding EA-D antigen, were detected. No EBER + cells were detected in other inflammatory or benign lymphoproliferative skin disorders tested. Polymerase chain reaction amplification confirmed the presence of EBV DNA sequences in five of six biopsy specimens from the patients.

Latent EBV infection is associated with the development of cutaneous lesions of HV.

ULTRAVIOLET LIGHT  

Hydroa vacciniforme.

Bickers DR, Demar LK, DeLeo V, Poh-Fitzpatrick MB, Aronberg JM, Harber LC.

Arch Dermatol 1978 Aug;114(8):1193-6 Abstract quote

Two patients with hydroa vacciniforme, a rare photodermatosis of unknown etiology, demonstrated distinctive scarring and vesiculobullous skin lesions on light-exposed body areas. Results of blood and urine porphyrin studies were normal, and no systemic abnormalities were noted. A small bullous lesion was produced in normal skin in case 1 with 15 times the minimal erythema dose of ultraviolet energy.

The conditions of both patients improved while they were taking beta carotene orally.

Hydroa vacciniforme: induction of lesions with ultraviolet A.

Halasz CL, Leach EE, Walther RR, Poh-Fitzpatrick MB.

J Am Acad Dermatol 1983 Feb;8(2):171-6 Abstract quote

Hydroa vacciniforme is a rare photosensitivity disorder with onset in childhood. The distinctive lesion is a vesicle which heals with scarring.

We report a case of hydroa vacciniforme in which an abnormal minimal erythema dose to wavelengths of 322 to 370 nm within the ultraviolet A (UVA) range was demonstrated. Vesicles could be induced only with multiple exposures to UVA. Increased tolerance to UVA erythema was induced by multiple UVB exposures, although tanning was poor. Of note were the presence of several halo nevi and a history of the loss of ability to tan.

The clinical features and appropriate laboratory evaluation of hydroa vacciniforme are reviewed.

Abnormally low UV-induced unscheduled DNA synthesis in cells from a patient with hydroa vacciniforme.

Andrews AD, Halasz CL, Poh-Fitzpatrick MB.

Photodermatol 1985 Oct;2(5):315-8 Abstract quote

Skin fibroblasts from a patient with the photosensitive disorder hydroa vacciniforme were tested in vitro for DNA repair capacity.

The rate of ultraviolet light (254 nm)-induced unscheduled DNA synthesis (UDS) in these fibroblasts was found to be 51-59% of the rate found in 4 normal fibroblasts strains.

The patient had none of the clinical signs of the classic DNA deficient disease, xeroderma pigmentosum.

Action spectrum for UV erythema and reproduction of the skin lesions in hydroa vacciniforme.

Sunohara A, Mizuno N, Sakai M, Kawabe Y, Sakakibara S.

Department of Dermatology, Nagoya City University Medical School, Japan.

Photodermatol 1988 Jun;5(3):139-45 Abstract quote

Action spectra for UV erythema and reproduction of the skin lesions in 4 patients with hydroa vacciniforme (HV) were studied.

Vesicles were successfully reproduced by repeated daily monochromatic irradiations of 330, 340, 350 and 360 nm for 5, 6 or 7 days. The daily doses were equivalent to global solar radiation for 70-190 min. The vesicles produced were identical to those of HV, macroscopically and histologically. Repeated daily exposures to a small dose of UVA produced vesicles, whereas a large but single exposure to UVA failed to do so. Daily exposures to UVB failed to produce the vesicles.

The minimal erythema dose (MED) was lower than the minimum limits of the normal persons in the 290-310 nm range.

 

LABORATORY/
RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
LABORATORY MARKERS All normal

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  
VARIANTS  
FAMILIAL  

Familial hydroa vacciniforme.

Gupta G, Mohamed M, Kemmett D.

Department of Dermatology, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, U.K.

Br J Dermatol 1999 Jan;140(1):124-6 Abstract quote

Hydroa vacciniforme is a rare, idiopathic photodermatosis with an onset in childhood and characterized by acute vesiculation, crusting and scarring following sun exposure. Familial cases are extremely rare with only one previous report.

We report a brother and sister, both of whom have developed hydroa vacciniforme.

EAR  

A case of hydroa vacciniforme with unusual ear mutilation.

Kim WS, Yeo UC, Chun HS, Lee ES.

Department of Dermatology, Sung kyun kwan University, College of Medicine, Samsung Medical Center, Seoul, Republic of Korea.

Clin Exp Dermatol 1998 Mar;23(2):70-2 Abstract quote

A 22 year-old man visited our department with a 18-year-history of recurrent vesicular eruption on his skin when exposed to the sun. History revealed that the skin lesions developed as vesicles at first, then over the next several days, they formed crusts and healed with scarring.

We were able to induce skin lesions by a repetitive UV-A provocation test. By the clinical and histologic features of the induced lesions, the case was diagnosed as hydroa vacciniforme (HV). However, no vesicular lesions were found on physical examination. Instead, in addition to varioliform scarring, we found various unusual clinical manifestations: burn-like lesions and crusts, flexion contracture of the digitum, and ear lobe mutilation.

The ear lobe mutilation, which had not been reported previously in HV, was especially interesting.

LATE ONSET  

Hydroa vacciniforme persistent in a 60-year-old man.

De Pietro U, Simoni R, Barbieri C, Girolomoni G. III

Division of Dermatology, Istituto Dermopatico dell'Immacolata, IRCCS, via Monti di Creta 104, 00167 Roma, Italy.

Eur J Dermatol 1999 Jun;9(4):311-2 Abstract quote

Hydroa vacciniforme (HV) is an idiopathic photodermatosis with onset in childhood, a chronic-recurrent course, and spontaneous resolution in adolescence or early adulthood.

We present a patient with typical HV in whom lesions began in childhood and continued until 60 years of age.

Late-onset hydroa vacciniforme: two case reports.

Wong SN, Tan SH, Khoo SW.

National Skin Centre, 1 Mandalay Road, Singapore 308205

Br J Dermatol 2001 Apr;144(4):874-7 Abstract quote

Hydroa vacciniforme (HV) is a rare blistering photodermatosis that heals with vacciniform scarring, with onset usually in childhood and spontaneous resolution by early adulthood.

We report two cases of HV seen at the National Skin Centre, Singapore, both with a late onset at 20 years of age, during compulsory military service, and one with a less typical non-vesicular presentation, that initially caused some diagnostic difficulties.

SCARRING, EXCESSIVE  

Hydroa vacciniforme: an unusual clinical manifestation.

Leenutaphong V.

Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

J Am Acad Dermatol 1991 Nov;25(5 Pt 2):892-5 Abstract quote

Hydroa vacciniforme is a rare, chronic photodermatosis with onset in childhood that is characterized by recurrent vesiculation, necrosis, and vacciniform scarring limited to sun-exposed skin.

We report a case of nonvesicular hydroa vacciniforme in which only extensive crusting associated with hypertrophic scarring on sun-exposed skin was present. Multiple exposures to UVA, however, reproduced lesions with the typical clinical and histologic features of hydroa vacciniforme. Results of blood, urine, and fecal porphyrin studies were normal

Hydroa vacciniforme with unusually severe scar formation: diagnosis by repetitive UVA phototesting.

Hann SK, Im S, Park YK, Lee S.

Department of Dermatology, Yonsei University Wonju College of Medicine, Kangwon-Do, Korea.

J Am Acad Dermatol 1991 Aug;25(2 Pt 2):401-3 Abstract quote

Hydroa vacciniforme is a rare, chronic, photosensitive disorder manifested in childhood by recurrent vesicles that heal with scarring.

Reproduction of vesicles with repetitive UVA phototesting may be an important diagnostic aid. Recurrent eruption resulted in severe scarring of the face and a flexion contracture of the finger in our patient.

The clinical features and laboratory evaluation of hydroa vacciniforme are reviewed.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
CUTANEOUS T-CELL LYMPHOMA (HYDROA-LIKE LYMPHOMA)  
Hydroa-like lymphoma with CD56 expression.

Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.

J Cutan Pathol. 2008 May;35(5):488-94. Abstract quote

Hydroa-like lymphoma is an extremely rare and aggressive lymphoma described in children from Latin American countries (Mexico, Guatemala and Peru) and Asia (Japan, Korea and Taiwan).

Clinically, patients present with vesicles, ulcers and scars occurring on both sun-exposed and non-sun-exposed areas. In contrast to classical hydroa vacciniforme, hydroa-like lymphoma is associated with systemic lymphoma of T-cell type that expresses either CD4 or CD8.

We report the findings from two unusual cases of hydroa-like lymphoma that, unlike the cases described thus far in the literature, express CD56 and resemble natural killer cell lymphomas. Two 9-year-old boys presented with clinical histories of waxing and waning ulcerative blistering lesions since 3 years of age. Histological examination of skin biopsies from both cases showed periappendigeal infiltrates of atypical lymphocytes. Immunohistochemical studies showed that the cells were highlighted by markers for CD3, CD56 and CD30, but did not express CD4 and CD8. Both patients were alive with disease 1 year later.

Hydroa-like lymphoma with natural killer-cell phenotype may have a similar outcome to T-cell derived hydroa-like lymphoma, but the prognosis appears to be better than classic NK lymphomas, which in general behave in an aggressive fashion.


Hydroa vacciniforme-like primary cutaneous CD8-positive T-cell lymphoma.

Chen HH, Hsiao CH, Chiu HC.

Department of Dermatology, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei, Taiwan.

Br J Dermatol 2002 Sep;147(3):587-91 Abstract quote

An 8-year-old Taiwanese girl had a 6-month history of a relapsing papulovesicular eruption on her face that resembled hydroa vacciniforme (HV).

Histologically, there was a dense infiltration of large atypical lymphocytic cells expressing CD8. TCR-gamma gene rearrangement study revealed a monoclonal band present in the DNA extracted from the specimen. A diagnosis of CD8+ cutaneous T-cell lymphoma (CTCL) was made. The patient was treated with Chinese herbal drugs and her skin lesions waxed and waned.

At this writing, 11 months after establishment of the diagnosis, the skin lesions have been limited to the facial area and no definite evidence of systemic involvement is noted. To our knowledge, this is the first case of CD8+ primary CTCL with clinical features resembling HV.

Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a distinctive type of cutaneous T-cell lymphoma.

Magana M, Sangueza P, Gil-Beristain J, Sanchez-Sosa S, Salgado A, Ramon G, Sangueza OP.

Department of Pediatric Dermatology, Hospital General de Mexico/University of Mexico (UNAM), Mexico DF.

J Am Acad Dermatol 1998 Apr;38(4):574-9 Abstract quote

BACKGROUND: Angiocentric cutaneous T-cell lymphomas of childhood (ACTCLC) are an unusual type of T-cell lymphomas that present with a vesiculopapular eruption mimicking hydroa vacciniforme. Most patients have been children from Asia and Latin America.

OBJECTIVE: The purpose of this study was to describe four cases of ACTCLC; to discuss its clinical, histopathologic, and immunohistochemical features; to consider its possible relationship to the Epstein-Barr virus (EBV); and to clarify its classification within the spectrum of angiocentric lymphomas.

METHODS: The clinical, histopathologic, and immunohistochemical features of four cases of ACTCLC were identified and analyzed. In addition in situ hybridization for EBV was performed in all cases.

RESULTS: The clinical features were similar to previous cases reported under different names, such as hydroa-like lymphomas, edematous, scarring vasculitic panniculitis. Histologically, all showed angiocentric infiltrates composed mainly of T cells. In all cases there were variable numbers of CD30+ cells. The EBV was present in three of the cases.

CONCLUSION: ACTCLC is a distinct type of T-cell lymphoma. It affects mainly children, and the EBV appears to play a role in the pathogenesis of this disease.

EDEMATOUS SCARRING VASCULITIC PANNICULITIS  

Edematous, scarring vasculitic panniculitis: a new multisystemic disease with malignant potential.

Ruiz-Maldonado R, Parrilla FM, Orozco-Covarrubias ML, Ridaura C, Tamayo Sanchez L, Duran McKinster C.

Department of Pediatric Dermatology, National Institute of Pediatrics, Mexico City, Mexico.

J Am Acad Dermatol 1995 Jan;32(1):37-44 Abstract quote

BACKGROUND: Hydroa vacciniforme (HV) is a disease of unknown origin characterized by erythema, vesicles, necrosis, and varicelliform scars in light-exposed skin. Systemic involvement is absent. A few patients have been reported with "severe HV" with systemic involvement, development of non-Hodgkin's lymphoma, and a poor prognosis.

OBJECTIVE: Our purpose was to characterize and differentiate our patients' disease from HV.

METHODS: We performed a retrospective clinicopathologic study of 14 children previously diagnosed as having "severe HV."

RESULTS: The extension and severity of the cutaneous lesions, fever, wasting, failure to thrive, hepatosplenomegaly, vasculitis, panniculitis, and potential development of lymphoma are features that clearly differentiate edematous scarring vasculitic panniculitis from HV.

CONCLUSION: Edematous scarring vasculitic panniculitis is a novel multisystemic disease with malignant potential that is not related to classic HV.

EPSTEIN-BARR VIRUS  

Epstein-Barr virus-associated recurrent necrotic papulovesicles with repeated bacterial infections ending in sepsis and death: consideration of the relationship between Epstein-Barr virus infection and immune defect.

Yoon TY, Yang TH, Hahn YS, Huh JR, Soo Y.

Department of Dermatology, College of Medicine & Medical Research Institute, Chungbuk National University, Cheongju, Korea.

J Dermatol 2001 Aug;28(8):442-7 Abstract quote

The disease of Epstein-Barr virus (EBV) -associated recurrent necrotic papulovesicles is a distinct clinicopathologic entity different from classic hydroa vacciniforme (HV). A few patients have been reported as atypical HV with systemic involvement, development of lymphoma, and poor prognosis.

We describe a patient with recurrent necrotic papulovesicles and multiple varioliform scars in both sun-exposed and covered areas. In contrast to cases of previously reported atypical HV, our patient suffered from repeated bacterial infections on various sites ending in sepsis and death, but without malignant transformation. EBV was detected in the lymphoid cells from the skin lesions by anti-latent membrane protein (LMP) antibody and in situ hybridization.

We suggest that the repeated bacterial infections in this case raise the possibility of an association of EBV infection with increased susceptibility to bacterial infections.

Epstein-Barr virus-associated peripheral T-cell lymphoma in adults with hydroa vacciniforme-like lesions.

Cho KH, Kim CW, Heo DS, Lee DS, Choi WW, Rim JH, Han WS.

Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.

Clin Exp Dermatol 2001 May;26(3):242-7 Abstract quote

We describe two Korean adult patients who had necrotizing papulovesicles mainly on their faces.

Skin biopsy specimens showed perivascular and periadnexal infiltrate of atypical lymphoid cells with vasculitis in the dermis and subcutaneous tissue. In situ hybridization demonstrated a latent infection of Epstein-Barr virus in the majority of lymphoid cells in the dermis.

These patients were diagnosed as having T-cell lymphoma. Interestingly, large granular lymphocytosis was found in the peripheral blood of Case 2.

LYMPHOMATOID PAPULOSIS  

Hydroa vacciniforme-like lymphomatoid papulosis in a Japanese child: a new subset.

Tabata N, Aiba S, Ichinohazama R, Kikuchi K, Aoyama H, Watanabe M, Tagami H.

Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.

J Am Acad Dermatol 1995 Feb;32(2 Pt 2):378-81 Abstract quote

An 8-year-old Japanese girl had a 9-month history of a self-healing papulovesicular eruption on her face, scalp, and neck that resembled hydroa vacciniforme (HV). Histologically, there was a dense infiltration of small lymphocytic cells and scattered large atypical cells expressing CD30. Study of gene rearrangement showed no monoclonality in the infiltrating cells.

To our knowledge, this is the second case of lymphomatoid papulosis with clinical features resembling HV. However, we also found descriptions in the literature of two other Japanese children with malignant lymphoma who both initially had clinical features resembling HV.

These findings suggest that these cases of HV-like disease constitute a subset of lymphomatoid papulosis that is highly likely to progress to malignant lymphoma.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  

Factors influencing the photo-reproduction of hydroa vacciniforme lesions.

Leroy D, Dompmartin A, Michel M, Tack B, Bravard P, Louvet S.

Department of Dermatology, Centre Hospitalier Universitaire, Caen, France.

Photodermatol Photoimmunol Photomed 1997 Jun;13(3):98-102 Abstract quote

Hydroa vacciniforme vesicles can be reproduced experimentally with repetitive UVA irradiations, but this photo-reproduction is not constant.

The aim of this study was to search for the factors that influence photo-reproduction. To reproduce hydroa vacciniforme lesions six patients underwent repetitive UVA and polychromatic irradiations on the back. In four patients out of six, UVA irradiation with high doses induced papulo-vesicular lesions. Photo-induced lesions were very close to those induced by sunlight. Photo-reproduction failed when phototesting was done after or shortly before remission.

Therefore, the absence of photo-reproduction appears to be a good prognostic factor.

Hydroa vacciniforme: A clinical and follow-up study of 17 cases.

Gupta G, Man I, Kemmett D.

Department of Dermatology, Western Infirmary, Glasgow, United Kingdom.

J Am Acad Dermatol 2000 Feb;42(2 Pt 1):208-13 Abstract quote

BACKGROUND: Hydroa vacciniforme (HV) is a rare, sporadic, idiopathic photodermatosis characterized by vesicles and crust formation after sunlight exposure. The lesions typically heal with vacciniform scarring.

OBJECTIVE: We identify and review the clinical features and follow-up data of Scottish patients with HV and report on the prevalence of this condition. This is the largest recent study of HV patients from a single center.

METHODS: In this retrospective study, patients with HV were identified by means of the diagnostic database from the Photobiology Unit, Dundee. Patients were contacted and details of clinical features, duration of disease, results of investigations, and treatment were recorded. At review, disease progress was assessed.

RESULTS: Between 1973 and 1997, 17 patients (9 males and 8 females) with a diagnosis of HV were investigated. Data from 15 patients showed a mean age at onset of 7.9 years (range, 1 to 16 years), with females (mean, 6.7 years; range, 2 to 12 years) having an earlier onset than males (mean, 8.7 years; range, 1 to 16 years). A bimodal age distribution was also identified with onsets between the ages of 1 and 7 years and 12 and 16 years. At review, spontaneous clearing had occurred in 9 patients (60%) with mean duration of disease being 9 years (range, 4 to 17 years). Males had longer disease duration (mean, 11 years; range, 5 to 17 years) than females (mean, 5 years; range, 4 to 7 years). Eight patients (53%) were sensitive in the UVA wave-band on monochromator phototesting, and 6 (40%) experienced papulovesicular lesions on repetitive broad-spectrum UVA irradiation. All patients received broad-spectrum sunscreens with variable results. Of the 5 patients treated with narrow-band UVB (TL-01) phototherapy, 3 reported beneficial results with an increase in tolerance to sunlight exposure and associated reduction in disease severity.

CONCLUSION: The estimated prevalence of HV was at least 0.34 cases per 100,000 with an approximately equal sex ratio. Males had a later onset and longer duration of disease than females. Phototesting showed abnormal responses in the UVA wavebands in 53% of cases, whereas 60% of patients treated with prophylactic TL-01 phototherapy found it beneficial.

TREATMENT  
CYCLOSPORINE  

Hydroa vacciniforme presenting in an adult successfully treated with cyclosporin A.

Blackwell V, McGregor JM, Hawk JL.

Department of Dermatology, Guy's Hospital, London, UK.

Clin Exp Dermatol 1998 Mar;23(2):73-6 Abstract quote

Hydroa vacciniforme (HV) is a rare photodermatosis first described by Bazin in the mid-nineteenth century. It typically presents in childhood and resolves during adolescence. Rarely, however, symptoms may persist into adult life.

We now describe a patient with this condition presenting unusually for the first time at the age of 58 years and responding to treatment with cyclosporin A.

FISH OILS  

Dietary fish oil as a photoprotective agent in hydroa vacciniforme.

Rhodes LE, White SI.

Department of Dermatology, Royal Liverpool University Hospital, U.K.

Br J Dermatol 1998 Jan;138(1):173-8 Abstract quote

Hydroa vacciniforme is a troublesome and scarring photosensitivity disorder for which treatment is unsatisfactory. Dietary fish oil rich in omega-3 polyunsaturated fatty acids reportedly increases the resistance to ultraviolet-induced erythema and rash provocation in polymorphic light eruption.

We report for the first time the response of hydroa vacciniforme to dietary fish oil. Three Caucasian boys with the condition were placed on MaxEPA, five capsules daily. Phototesting was performed at baseline and after 3 months supplementation. At baseline, low erythemal thresholds were seen to monochromated UVA at 350 and 370 nm in all three boys, while one also had a low threshold to 320 nm (UVA) and another showed a low threshold to 300 nm (UVB). Broad-band UVA provocation challenge produced typical skin lesions in all the subjects. Following fish oil, all the boys showed reduced erythemal sensitivity to UVA and one also showed reduced sensitivity to UVB. Provocation challenge revealed a reduced response in all three children.

Clinically, these changes were accompanied by pronounced improvement in one child, mild improvement in the second child, but no improvement in the third. The third boy subsequently showed good clinical response to azathioprine

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