Disseminated Bacille Calmette‐Guérin infection in a patient with severe combined immunodeficiency caused by JAK3 gene mutation

Bacille Calmette‐Guérin (BCG), a live attenuated vaccine prepared using Mycobacterium bovis, can prevent tuberculosis in children and is routinely administered to infants in China and many other countries. A serious complication following vaccination is disseminated BCG infection. The risk is greatly increased in patients with severe combined immunodeficiency disease (SCID), a syndrome characterized by deficiency of both humoral and cellular immunity. We report a case of disseminated BCG infection in an infant with SCID caused by two novel janus kinase 3 (JAK3) gene mutations.     

Lupus vulgaris: report of two cases

Although there has been a steady decline in the incidence of tuberculosis in recent years, it persists in some regions, and where AIDS is especially prevalent, the number of new cases has been increasing. Thus, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multidrug-resistant pulmonary tuberculosis. Lupus vulgaris has been and remains the most common form of cutaneous tuberculosis. Cutaneous manifestations of disseminated tuberculosis are unusual, being seen in less than 0.5% of cases. Scrofuloderma, tuberculosis verrucosa cutis and lupus vulgaris comprise most cutaneous tuberculosis cases. Bacillus Calmette-Guerin (BCG) is derived from an attenuated strain of Mycobacterium bovis and is employed beneficially as a relatively safe vaccination in Poland and other countries in which the prevalence of tuberculosis is high. However, BCG vaccination may produce complications, including disseminated BCG and lupus vulgaris, the latter seen in one of our two patients in whom lupus vulgaris at the inoculation site followed a second vaccination with BCG 12 years after the initial one. A similar phenomenon has been described after immunotherapy with BCG vaccination. Re-infection (secondary) inoculation cutaneous tuberculosis may also occur as a result of BCG vaccination, producing either lupus vulgaris or tuberculosis verrucosa cutis, probably depending upon the patient's degree of cell-mediated immunity. However, most lupus vulgaris cases are not associated with vaccination with BCG, as occurred in our first patient. For those who do develop lupus vulgaris, it can be persistent for a long period, in some cases for many decades. In the second patient we describe a lengthy duration and cutaneous reactivation at distant sites after more than 40 years.     

Persistent Bacillus Calmette–Guerin Reaction: A Potential Clue to Underlying Immune Deficiency

Bacillus Calmette–Guerin (BCG) vaccine complications in patients with severe combined immunodeficiency (SCID) have been well documented in the literature. We present a case in which the BCG vaccine was administered to an infant who was later diagnosed with SCID and presented with worsening localized BCG reaction upon arrival in the United States. Although the BCG vaccine is not routinely administered in the United States, it is important for physicians to be aware of potential complications of BCG vaccination since prompt treatment can be lifesaving.     

Erythema induratum of Bazin in an infant after Bacille Calmette-Guerin vaccination

We report the first case of erythema induratum of Bazin (EIB) after Bacille Calmette-Guerin (BCG) vaccination in an infant. The patient developed recurrent multiple erythematous and subcutaneous nodules on his legs 2 months after a BCG vaccination. He had no other symptoms or family history of tuberculosis (TB). Histopathological findings revealed a granulomatous lobular panniculitis. EIB often appears as a chronic, nodular eruptions that frequently occur on the lower legs of females with tuberculin hypersensitivity. To date, only a few cases of infants with EIB have been reported. There have been no clinical reports of EIB after BCG vaccination. Our case suggests that Mycobacterium bovis in the BCG vaccination may have caused EIB.     

Disseminated BCG infection revealing X-linked severe combined immunodeficiency

BACKGROUND: Live attenuated Bacillus Calmette-Guérin (BCG) vaccine is rarely responsible for disseminated infection. We report a case of X-linked severe combined immunodeficiency (SCID) revealed by a disseminated skin infection. PATIENTS AND METHODS: A 4-month-old baby was hospitalized for prolonged gastroenteritis. He was in poor general condition, with prolonged fever, oral and gluteal candidiasis and purple nodules associated with ulceration of the BCG scar. The absence of a thymus, T-cells and NK-cells, and the presence of nonfunctional B-lymphocytes led to a diagnosis of SCID. Biopsies of nodules revealed a dermal infiltrate without necrosis. A Ziehl-Neelson stain was highly positive and the culture grew Mycobacterium bovis. Treatment consisted of a four-drug antibiotic regimen directed against M. bovis combined with gamma interferon, immunoglobulins and antibiotic prophylaxis by cotrimoxazole and was followed by a haploid-identical bone marrow transplant without rejection at six months. The early death of the child's maternal uncle from sepsis suggested X-linked transmission, which was subsequently confirmed by genetic analysis. DISCUSSION: BCG vaccination can cause serious infections in immunocompromised subjects. Skin involvement is extremely rare but may be the first sign of SCID, of which the X-linked form is the most common and corresponds to a variety of mutations in the gene coding for the gamma chain common to several interleukin receptors. Genetic counselling is essential to identify female carriers and allow early antenatal diagnosis. Bone marrow transplantation is the only treatment.     

Disseminated cutaneous bacille Calmette-Guérin infection identified by polymerase chain reaction in a patient with X-linked severe combined immunodeficiency

An 8-month-old boy developed a disseminated cutaneous mycobacterial infection at 6 months of age that responded poorly to treatment. Further immunologic study and sequence analysis showed the presence of a missense mutation in the IL2RG gene, and X-linked severe combined immunodeficiency was diagnosed. To identify the strain of the microorganism causing the cutaneous infection, polymerase chain reaction with four pairs of primers was performed on skin biopsy specimens positive for acid-fast bacilli. Sequence analysis showed 99.36% homology with a bacilli Calmette-Guérin positive control. Disseminated bacilli Calmette-Guérin disease must be considered in any infant with cutaneous mycobacterial lesions, especially those with atypical histologic findings or who are immunocompromised. Testing by polymerase chain reaction using the proper primers may help in making a precise diagnosis.     

Chronic exanthema in a child with congenital rubella

BACKGROUND: Since congenital rubella has become extremely uncommon following the introduction of rubella vaccination, cutaneous signs are currently rarely reported. PATIENTS AND METHODS: An infant, presenting congenital rubella (seroconversion of the mother for rubella at 11 weeks' amenorrhoea), presented diffuse exanthema between the ages of seven and 24 months. In a setting of congenital rubella syndrome, the infant presented psychomotor retardation, deafness, hypoplasia of the pulmonary artery and under-nourishment. Humoral and cell-mediated immunodeficiency was also noted. DISCUSSION: The cutaneous signs of congenital rubella were first described in the 1960s and 1970s; they are rare and appear after a symptom-free period before resolving spontaneously several months later. Standard findings include chronic exanthema of the face and extremities associating reticulated erythema and pigmented macular papules. Exanthema indicates chronic and persistent viral infection, a common situation in newborn babies and infants following maternal-foetal infection. The persistence of viral infection in infants is attributed to immature cellular immunity, which would otherwise either eradicate the virus or ensure passage to the latency phase. In the present case, there was also relative humoral immunodeficiency resulting from foetal rubella infection. The symptom-free interval before the onset of rash and other clinical signs may be due to the relative transient protection afforded by the presence of maternal immunoglobulines G.     

Primary Cutaneous Mucormycosis in an Extremely Preterm Infant Successfully Treated with Liposomal Amphotericin B

Cutaneous mucormycosis is a rare but often fatal invasive fungal infection that occurs most commonly in patients with diabetes, malignancy, and other immunocompromising conditions. We report an extremely preterm (<28 weeks) baby boy who developed polymicrobial sepsis and primary cutaneous mucormycosis within his first 10 days of life. He was successfully treated with medical management alone since he was not a candidate for surgery. Successful treatment of cutaneous mucormycosis without surgical debridement has been reported on only two other occasions. This case highlights the importance of rapid and thorough evaluation of skin lesions when evaluating preterm infants and other immunocompromised patients, even when other sources of infection have been identified.     

Acute Graft-versus-Host Disease with Unusual Cutaneous Intracellular Vacuolation in an Infant with Severe Combined Immunodeficiency

Abstract: We report an infant with severe combined immunodeficiency (SCID) who had cutaneous manifestations of acute graft-versus-host disease (GVHD) due to maternofetal lymphocyte engraftment. Histologic and ultrastructural examinations of the skin revealed intracellular vacuoles resembling lipid droplets in the epidermis and dermis, which is not a recognized feature of acute GVHD or SCID.     

Two cases of primary cutaneous nocardiosis caused by intralesional injection

Nocardiosis is a rare localized or systemic suppurative disease caused by the actinomycete Nocardia species. The respiratory tract is the most common site of infection, but primary cutaneous nocardiosis can also be induced by direct inoculation. Nocardiosis is usually reported in immunocompromised patients, such as those with human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease, autoimmune diseases, cancer, or in those who have had organ transplantation or corticosteroid administration. However, it can also affect individuals with no serious underlying condition. We reported two cases of primary cutaneous nocardiosis in immunocompetent patients after intralesional injection of steroid.     

Kaposi sarcoma in association with molluscum contagiosum: an uncommon diagnosis in a single biopsy and potential diagnostic pitfall

Molluscum contagiosum is a cutaneous poxviral infection that is rarely associated with other skin diseases, such as cutaneous neoplasms. Such associations are likely to be coincidental, except in immunocompromised patients. Kaposi sarcoma, an angioproliferative neoplasm derived from lymphatic endothelium, is mediated by human herpes virus-8 infection and occurs with increased frequency in immunocompromised individuals. We report an unusual case of molluscum contagiosum with underlying cutaneous Kaposi sarcoma diagnosed in a single skin biopsy of a human immunodeficiency virus-positive patient. Our case highlights the importance of adequate sampling to avoid missing secondary diagnoses in histopathologic sections and alerts pathologists and dermatologists to the possibility of coinfection in high-risk patients by 2 virally-mediated skin conditions.     

Cutaneous Lesions as a Clue to Servere Combined Immunodeficiency

A 2-month-old boy experienced cutaneous lesions that revealed an underlying severe, combined immunodeficiency (SCID). It is important to recognize cutaneous manifestations of primary immunodeficiency disorders, as they may provide the earliest clue to a defect in immune function.     

Pyoderma gangrenosum-like ulcer caused by Helicobacter cinaedi in a patient with x-linked agammaglobulinaemia

Cutaneous lesions of the legs have been linked to Helicobacter species in a number of patients with X-linked agammaglobulinaemia (XLA), a primary immunodeficiency. We describe a 26-year-old patient with XLA, who was referred with an extensive skin ulcer that enlarged gradually over the course of 7 years. The ulcer resembled pyoderma gangrenosum (PG), and extended from below the knee to the ankle. The man (who has sex with men) was negative for human immunodeficiency virus. Helicobacter cinaedi was identified by 16S ribosomal (r)DNA PCR analysis from a biopsy of the lesion. This fastidious organism has been implicated previously in causing unexplained skin macules in one other patient with XLA. We suggest that early consideration of infection with Helicobacter species in immunocompromised patients who present with unexplained cutaneous lesions is important, as a prolonged antibiotic course can lead to clinical improvement.     

Extensive Tinea in a Patient With Severe Combined Immunodeficiency

Abstract:   Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders characterized by a defect of T and B cell immunity with a genetic origin in most cases. Although the X-linked recessive form is most common (60–70%), there are autosomal recessive forms (20%) and spontaneous mutations. While SCID may present with many nosocomial infections, dermatophyte infections are not common. We reported a case of SCID which was associated with a widespread skin infection with Trichophyton mentagrophytes .     

Characteristics of cutaneous cytomegalovirus infection in non-acquired immune deficiency syndrome, immunocompromised patients

BACKGROUND: Although cytomegalovirus (CMV) disease is a severe complication among immunocompromised patients, its cutaneous features have not been frequently reported. As herpes simple virus (HSV) infection commonly develops in CMV skin lesions, a study is needed on the pathogenetic role of CMV in cutaneous lesion formation. OBJECTIVES: The purpose of this study is to characterize the clinical and histopathological features of cutaneous CMV infection and to determine whether CMV plays a true pathogenetic role in cutaneous lesions, or if it is just an innocent bystander during HSV infection among non-AIDS (acquired immune deficiency syndrome), immunocompromised patients. PATIENTS AND METHODS: A total of nine human immunodeficiency virus-negative patients diagnosed with cutaneous CMV infection from July 1999 to February 2005 at Samsung Medical Center were analysed in terms of their clinical and histopathological characteristics. In addition, we examined for the co-presence of HSV by performing immunohistochemical analysis and polymerase chain reaction. RESULTS: All the patients were immunocompromised; five had haematological diseases and four were organ transplant recipients. The clinical and histopathological features were similar to those of previous studies of patients with AIDS. Multiple anogenital ulcerations were the most frequent cutaneous presentation (66.7%). Most cytopathic changes were found in the dermis, particularly within the vascular endothelial cells (77.8%) and macrophages (66.7%). However, the association of CMV with concurrent HSV infection was even lower than that seen in patients with AIDS. Only one patient revealed a co-existing cutaneous HSV infection. CONCLUSIONS: In non-AIDS individuals, the cutaneous lesions from CMV infection showed similar clinical and histopathological features to those of patients with AIDS. However, skin lesions may not be highly associated with HSV, and CMV does seem to contribute to lesion development as a cutaneous manifestation among the CMV infected, non-AIDS, immunocompromised patients.     

Cutaneous infection due to acremonium

We report an immunocompromised patient who developed a cutaneous infection caused by acremonium which is a rare opportunistic fungi. With the increasing number of immunocompromised patients opportunistic fungal infection can cause serious diseases and early recognition is mandatory.     

Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome.

BACKGROUND--Aspergillosis in patients with the acquired immunodeficiency syndrome is unusual, and the clinicopathologic features of primary cutaneous aspergillosis in this setting are undefined. Our findings show that the manifestations can differ from those of primary cutaneous aspergillosis in other immunocompromised patients. OBSERVATIONS--Two men with the acquired immunodeficiency syndrome developed foci of primary cutaneous aspergillosis beneath adhesive tape near central venous catheter sites. Typical lesions were flesh-colored to pink, umbilicated papules that clinically resembled molluscum contagiosum. Biopsy specimens showed variably ruptured follicles that contained collections of fungal hyphae typical of Aspergillus species. Cultures in one case identified Aspergillus fumigatus. The use of nonocclusive dressings and local wound care resulted in involution of several lesions. CONCLUSIONS--Primary cutaneous aspergillosis begins as saprophytic involvement of hair follicles secondary to the altered microenvironment beneath adhesive tape. Systemic antifungal therapy is prudent, but in the absence of neutropenia or other traditional risk factors for dissemination, it appears that Aspergillus in patients with the acquired immunodeficiency syndrome can produce relatively indolent cutaneous lesions with a tendency to resolve once precipitating factors are removed.     

Cutaneous cytomegalovirus infection in a patient with acquired immunodeficiency syndrome

Cytomegalovirus (CMV) infection in immunocompromised patients is a common opportunistic systemic infection which can lead to death, and usually presents with visceral manifestations, especially of the lung, brain, eye, and gastrointestinal tract. Cutaneous CMV infection is, however, relatively rare in immunocompromised patients. Cutaneous CMV infection can have variable clinical and histologic manifestations, and thus can be easily missed. We report a case of cutaneous CMV infection in a patient with acquired immunodeficiency syndrome, presenting as a generalized, pruritic, erythematous, maculopapular eruption.     

Epstein-Barr virus-associated leiomyosarcoma with cutaneous involvement in an African child with human immunodeficiency virus: a case report and review of the literature

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) are infrequently encountered lesions restricted to immunocompromised patients. However, they represent the second most common tumor in children with human immunodeficiency virus (HIV) infection. We report a case of a progressively enlarging abdominal mass with cutaneous involvement in an HIV-infected, 4-year-old African girl in Malawi with clinical acquired immunodeficiency syndrome on highly active antiretroviral therapy. Analysis of an excisional specimen revealed a well-differentiated leiomyosarcoma and subsequent studies revealed diffuse nuclear positivity for Epstein-Barr virus early RNAs in lesional cells. We present a report of this case and provide a summary of the literature regarding SMTs in pediatric HIV-infected patients. In addition, we draw attention to the cutaneous manifestations of SMTs in immunosuppressed populations. We highlight EBV-related SMTs as a potential cutaneous complication of HIV infection in children and immunosuppressed patients populations as a whole.