Yasmin Amir, MD

To the Editor:

Hailey-Hailey disease (HHD)(also known as familial benign chronic pemphigus) is an inherited autosomal-dominant condition in the family of chronic bullous diseases. It is characterized by flaccid blisters, erosions, and macerated vegetative plaques with a predilection for intertriginous sites. Lesions often are weeping, painful, pruritic, and malodorous, leading to decreased quality of life for patients. Complications of this chronic disease include an increased risk for secondary infection and malignant transformation to squamous cell carcinoma.¹

Treatment of HHD remains difficult. Topical steroids, oral steroids, and ablative techniques such as dermabrasion and ablative lasers are the most widely reported therapies. OnabotulinumtoxinA has been described as a successful treatment for patients with HHD, including for disease recalcitrant to other therapies.² We describe 2 patients with HHD who responded to treatment with intralesional onabotulinumtoxinA injections with and without adjuvant oral glycopyrrolate.

A 54-year-old woman presented with painful flaccid blisters under the breasts (Figure 1A) and in the axillae and groin of 3 weeks’ duration. Biopsy results from this initial visit were consistent with a diagnosis of HHD. The patient reported that the onset of blisters coincided with episodes of severe hyperhidrosis. Therapy with topical and oral steroids, antifungals, antibiotics, and topical aluminum chloride failed to achieve adequate disease control. After a discussion of the risks and benefits, the patient agreed to treatment with injections of onabotulinumtoxinA. At months 0, 3, and 6, the patient received 50 U of onabotulinumtoxinA under the breasts and in the axillae and the groin, for a total of 250 U each session. Each injection consisted of 2.5 U of onabotulinumtoxinA spaced 1-cm apart. Clinical improvement was noted within 2 weeks of initiating neuromodulator therapy. Follow-up at 9 months demonstrated improvement (Figure 1B); however, complete clearance was not achieved, and the patient required ongoing treatment with onabotulinumtoxinA every 3 months.

A 43-year-old woman presented with erythematous eroded plaques of the antecubital fossae, axillae, and chest (Figure 2A) of 10 years’ duration. A biopsy from an outside provider demonstrated findings consistent with a diagnosis of HHD. Prior therapies included topical and oral steroids. After a discussion of the risks and benefits, the patient was treated with onabotulinumtoxinA injections in combination with oral glycopyrrolate 5 mg daily. She received 30 U of onabotulinumtoxinA to each axilla, 10 U to each antecubital fossa, and 20 U to the central chest. At 1 month follow-up, the patient reported great improvement in lesion burden and active disease (Figure 2B). Nine months after treatment, her HHD was in complete remission with glycopyrrolate alone and she did not require further therapy with onabotulinumtoxinA.

Hailey-Hailey disease has been attributed to mutations of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1, that lead to aberrations in calcium signaling and subsequent impaired adhesion between keratinocytes.² These compromised cell-cell connections are worsened by the presence of humidity, causing further acantholysis. Chemical denervation of the sweat glands with botulinum toxin has been postulated to improve HHD by reducing moisture in vulnerable areas. Our 2 cases add to the existing literature documenting tangible clinical results that correlate with this hypothesis.^3-5

Our second case is unique in that the patient achieved rapid improvement using a combination of onabotulinumtoxinA and glycopyrrolate therapy. Both onabotulinumtoxinA and glycopyrrolate inhibit acetylcholine signaling that is required for sweat production; however, each drug exerts its effect on different zones of the cholinergic pathway, which may partially account for the synergistic effect of onabotulinumtoxinA and glycopyrrolate to improve HHD, as sweating is dually inhibited by the 2 drugs. Additionally, the combined local and systemic administration of these anticholinergic medications may further potentiate the sweat blockade, particularly in areas most prone to disease.

Botulinum toxin for the treatment of HHD is an effective monotherapy. The addition of an oral anticholinergic to local neuromodulator injections may speed symptom resolution and sustain disease remission. Further studies to evaluate this combination are warranted.

To the Editor:

Hailey-Hailey disease (HHD)(also known as familial benign chronic pemphigus) is an inherited autosomal-dominant condition in the family of chronic bullous diseases. It is characterized by flaccid blisters, erosions, and macerated vegetative plaques with a predilection for intertriginous sites. Lesions often are weeping, painful, pruritic, and malodorous, leading to decreased quality of life for patients. Complications of this chronic disease include an increased risk for secondary infection and malignant transformation to squamous cell carcinoma.¹

Treatment of HHD remains difficult. Topical steroids, oral steroids, and ablative techniques such as dermabrasion and ablative lasers are the most widely reported therapies. OnabotulinumtoxinA has been described as a successful treatment for patients with HHD, including for disease recalcitrant to other therapies.² We describe 2 patients with HHD who responded to treatment with intralesional onabotulinumtoxinA injections with and without adjuvant oral glycopyrrolate.

A 54-year-old woman presented with painful flaccid blisters under the breasts (Figure 1A) and in the axillae and groin of 3 weeks’ duration. Biopsy results from this initial visit were consistent with a diagnosis of HHD. The patient reported that the onset of blisters coincided with episodes of severe hyperhidrosis. Therapy with topical and oral steroids, antifungals, antibiotics, and topical aluminum chloride failed to achieve adequate disease control. After a discussion of the risks and benefits, the patient agreed to treatment with injections of onabotulinumtoxinA. At months 0, 3, and 6, the patient received 50 U of onabotulinumtoxinA under the breasts and in the axillae and the groin, for a total of 250 U each session. Each injection consisted of 2.5 U of onabotulinumtoxinA spaced 1-cm apart. Clinical improvement was noted within 2 weeks of initiating neuromodulator therapy. Follow-up at 9 months demonstrated improvement (Figure 1B); however, complete clearance was not achieved, and the patient required ongoing treatment with onabotulinumtoxinA every 3 months.

A 43-year-old woman presented with erythematous eroded plaques of the antecubital fossae, axillae, and chest (Figure 2A) of 10 years’ duration. A biopsy from an outside provider demonstrated findings consistent with a diagnosis of HHD. Prior therapies included topical and oral steroids. After a discussion of the risks and benefits, the patient was treated with onabotulinumtoxinA injections in combination with oral glycopyrrolate 5 mg daily. She received 30 U of onabotulinumtoxinA to each axilla, 10 U to each antecubital fossa, and 20 U to the central chest. At 1 month follow-up, the patient reported great improvement in lesion burden and active disease (Figure 2B). Nine months after treatment, her HHD was in complete remission with glycopyrrolate alone and she did not require further therapy with onabotulinumtoxinA.

Hailey-Hailey disease has been attributed to mutations of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1, that lead to aberrations in calcium signaling and subsequent impaired adhesion between keratinocytes.² These compromised cell-cell connections are worsened by the presence of humidity, causing further acantholysis. Chemical denervation of the sweat glands with botulinum toxin has been postulated to improve HHD by reducing moisture in vulnerable areas. Our 2 cases add to the existing literature documenting tangible clinical results that correlate with this hypothesis.^3-5

Our second case is unique in that the patient achieved rapid improvement using a combination of onabotulinumtoxinA and glycopyrrolate therapy. Both onabotulinumtoxinA and glycopyrrolate inhibit acetylcholine signaling that is required for sweat production; however, each drug exerts its effect on different zones of the cholinergic pathway, which may partially account for the synergistic effect of onabotulinumtoxinA and glycopyrrolate to improve HHD, as sweating is dually inhibited by the 2 drugs. Additionally, the combined local and systemic administration of these anticholinergic medications may further potentiate the sweat blockade, particularly in areas most prone to disease.

Botulinum toxin for the treatment of HHD is an effective monotherapy. The addition of an oral anticholinergic to local neuromodulator injections may speed symptom resolution and sustain disease remission. Further studies to evaluate this combination are warranted.

To the Editor:

Hailey-Hailey disease (HHD)(also known as familial benign chronic pemphigus) is an inherited autosomal-dominant condition in the family of chronic bullous diseases. It is characterized by flaccid blisters, erosions, and macerated vegetative plaques with a predilection for intertriginous sites. Lesions often are weeping, painful, pruritic, and malodorous, leading to decreased quality of life for patients. Complications of this chronic disease include an increased risk for secondary infection and malignant transformation to squamous cell carcinoma.¹

Treatment of HHD remains difficult. Topical steroids, oral steroids, and ablative techniques such as dermabrasion and ablative lasers are the most widely reported therapies. OnabotulinumtoxinA has been described as a successful treatment for patients with HHD, including for disease recalcitrant to other therapies.² We describe 2 patients with HHD who responded to treatment with intralesional onabotulinumtoxinA injections with and without adjuvant oral glycopyrrolate.

A 54-year-old woman presented with painful flaccid blisters under the breasts (Figure 1A) and in the axillae and groin of 3 weeks’ duration. Biopsy results from this initial visit were consistent with a diagnosis of HHD. The patient reported that the onset of blisters coincided with episodes of severe hyperhidrosis. Therapy with topical and oral steroids, antifungals, antibiotics, and topical aluminum chloride failed to achieve adequate disease control. After a discussion of the risks and benefits, the patient agreed to treatment with injections of onabotulinumtoxinA. At months 0, 3, and 6, the patient received 50 U of onabotulinumtoxinA under the breasts and in the axillae and the groin, for a total of 250 U each session. Each injection consisted of 2.5 U of onabotulinumtoxinA spaced 1-cm apart. Clinical improvement was noted within 2 weeks of initiating neuromodulator therapy. Follow-up at 9 months demonstrated improvement (Figure 1B); however, complete clearance was not achieved, and the patient required ongoing treatment with onabotulinumtoxinA every 3 months.

A 43-year-old woman presented with erythematous eroded plaques of the antecubital fossae, axillae, and chest (Figure 2A) of 10 years’ duration. A biopsy from an outside provider demonstrated findings consistent with a diagnosis of HHD. Prior therapies included topical and oral steroids. After a discussion of the risks and benefits, the patient was treated with onabotulinumtoxinA injections in combination with oral glycopyrrolate 5 mg daily. She received 30 U of onabotulinumtoxinA to each axilla, 10 U to each antecubital fossa, and 20 U to the central chest. At 1 month follow-up, the patient reported great improvement in lesion burden and active disease (Figure 2B). Nine months after treatment, her HHD was in complete remission with glycopyrrolate alone and she did not require further therapy with onabotulinumtoxinA.

Hailey-Hailey disease has been attributed to mutations of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1, that lead to aberrations in calcium signaling and subsequent impaired adhesion between keratinocytes.² These compromised cell-cell connections are worsened by the presence of humidity, causing further acantholysis. Chemical denervation of the sweat glands with botulinum toxin has been postulated to improve HHD by reducing moisture in vulnerable areas. Our 2 cases add to the existing literature documenting tangible clinical results that correlate with this hypothesis.^3-5

Our second case is unique in that the patient achieved rapid improvement using a combination of onabotulinumtoxinA and glycopyrrolate therapy. Both onabotulinumtoxinA and glycopyrrolate inhibit acetylcholine signaling that is required for sweat production; however, each drug exerts its effect on different zones of the cholinergic pathway, which may partially account for the synergistic effect of onabotulinumtoxinA and glycopyrrolate to improve HHD, as sweating is dually inhibited by the 2 drugs. Additionally, the combined local and systemic administration of these anticholinergic medications may further potentiate the sweat blockade, particularly in areas most prone to disease.

Botulinum toxin for the treatment of HHD is an effective monotherapy. The addition of an oral anticholinergic to local neuromodulator injections may speed symptom resolution and sustain disease remission. Further studies to evaluate this combination are warranted.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.¹ Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.² We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.

A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.

Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.

Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.

To the Editor:

Kaposi sarcoma (KS) is an angioproliferative tumor of endothelial origin associated with human herpesvirus 8 infection. It is one of the most prevalent opportunistic infections associated with AIDS and is considered an AIDS-defining illness. In the general population, the incidence of KS is 1 in 100,000 worldwide.¹ At the onset of the human immunodeficiency virus (HIV) epidemic in the early 1980s, 25% of individuals with AIDS were found to have KS at the time of AIDS diagnosis. Beginning in the mid-1980s and early 1990s with the introduction of highly active antiretroviral therapy (HAART), the incidence of KS declined to 2% to 4%,² likely secondary to restoration of immune response.³

The clinical course of KS ranges from benign to severe, involving both cutaneous and visceral forms of disease. Cutaneous KS is the most common form of disease and typically characterizes the initial presentation. It is classically described as violaceous patches, papules, or plaques that can become confluent, forming larger tumors over time. Biopsy of cutaneous lesions may vary based on the clinical morphology. The patch stage typically is characterized by abnormal proliferating vessels surrounding larger ectatic vessels.⁴ Vascular spaces are more jagged and lined by thin endothelial cells extending into the dermis, forming the classic promontory sign.⁵ In the plaque stage, the vascular infiltrate becomes more diffuse, involving the dermis and subcutis, and there is proliferation of spindle cells.⁴ In the nodular stage, spindle-shaped tumor cells form fascicles and vascular spaces become more dilated.^4,5 Advanced lesions are further associated with hyaline globules staining positive with periodic acid–Schiff.⁴ Lymphocytes, plasma cells, and hemosiderin-laden macrophages are admixed within this pathologic architecture.^4,5

Visceral KS most commonly occurs in the oropharynx, respiratory tract, and gastrointestinal tract, and rarely is the initial presentation of disease. Classically, visceral KS is an aggressive, potentially life-threatening form of disease and has been found to have a much worse prognosis than cutaneous KS alone. Pulmonary involvement is the second most common site of extracutaneous KS and is known as the most severely life-threatening form of disease.¹ Interestingly, since the advent of HAART, the incidence of KS with involvement of the visceral organs has declined at a more dramatic rate than cutaneous KS alone.³ Therefore, although more aggressive in nature, KS with visceral features has become increasingly rare and should be largely preventable given advances in AIDS therapy. We present a case of advanced AIDS-related KS with pulmonary involvement that is rarely seen after the advent of HAART.

A 39-year-old man with HIV diagnosed 8 years prior presented with fever, chest pain, progressive dyspnea, and hemoptysis of 5 months’ duration. At the time, he was nonadherent to medications and had poor follow-up with primary care physicians. At presentation he was tachycardic (149 beats per minute), tachypneic (26 breaths per minute), and his oxygen saturation was 80% on room air. Physical examination of the skin revealed asymptomatic violaceous penile lesions that the patient reported had been present for the last 8 months (Figure 1). Pertinent laboratory values included an HIV-1 viral load of 480,135 copies/mL (reference range, <20 copies/mL) and CD4 count of 14 cells/mm³ (reference range, 480–1700 cells/mm³). A chest radiograph was obtained and revealed bibasilar opacities compatible with a pleural and/or parenchymal process. Bronchoscopy was then performed and revealed bloody secretions throughout the tracheobronchial tree.

Histologic examination of biopsies of the penile lesions revealed spindle cell proliferation with hemorrhage (Figure 2A) that stained positively for HHV-8 (Figure 2B), consistent with KS. Biopsies taken during bronchoscopy similarly revealed spindle cells with hemorrhage (Figure 3). The patient was diagnosed with AIDS-related KS with visceral involvement of the lung parenchyma and tracheobronchial tree. The patient was then admitted to the medical intensive care unit and intubated. Therapy with HAART and paclitaxel was initiated. After 7 days of poor response to therapy, the family opted for terminal extubation and comfort care measures. The patient died hours later.

It is evident that treatment of AIDS patients with HAART is not only first-line therapy for the disease but also the best preventative measure against development of KS. Management of KS also centers around the initiation of HAART if the patient is not already maintained on the proper therapy.⁸ In addition to HAART, treatment options for visceral KS include a variety of chemotherapeutic agents, including but not limited to the use of single-agent adriamycin, vinblastine, paclitaxel, and thalidomide, or combination therapies.

Although notable advances have been made in the management of AIDS patients, this case highlights the need for clinicians to be aware of the risk for KS in the context of immunocompromise. Specifically, patients with advanced AIDS who are not adherent to HAART or who have a poor response to therapy have an amplified risk for developing KS in general as well as an increased risk for developing more severe visceral KS. Maintenance of patients with HAART is shown to greatly reduce the risk for both cutaneous and visceral KS; therefore, patient adherence with therapy is of utmost importance in preventing the occurrence of this deadly disease and its complications. Appropriate follow-up should be made, ensuring that these patients at high risk are adherent to therapy and have proper access to medical care to allow for prevention and early identification of potential complications.

To the Editor:

Kaposi sarcoma (KS) is an angioproliferative tumor of endothelial origin associated with human herpesvirus 8 infection. It is one of the most prevalent opportunistic infections associated with AIDS and is considered an AIDS-defining illness. In the general population, the incidence of KS is 1 in 100,000 worldwide.¹ At the onset of the human immunodeficiency virus (HIV) epidemic in the early 1980s, 25% of individuals with AIDS were found to have KS at the time of AIDS diagnosis. Beginning in the mid-1980s and early 1990s with the introduction of highly active antiretroviral therapy (HAART), the incidence of KS declined to 2% to 4%,² likely secondary to restoration of immune response.³

The clinical course of KS ranges from benign to severe, involving both cutaneous and visceral forms of disease. Cutaneous KS is the most common form of disease and typically characterizes the initial presentation. It is classically described as violaceous patches, papules, or plaques that can become confluent, forming larger tumors over time. Biopsy of cutaneous lesions may vary based on the clinical morphology. The patch stage typically is characterized by abnormal proliferating vessels surrounding larger ectatic vessels.⁴ Vascular spaces are more jagged and lined by thin endothelial cells extending into the dermis, forming the classic promontory sign.⁵ In the plaque stage, the vascular infiltrate becomes more diffuse, involving the dermis and subcutis, and there is proliferation of spindle cells.⁴ In the nodular stage, spindle-shaped tumor cells form fascicles and vascular spaces become more dilated.^4,5 Advanced lesions are further associated with hyaline globules staining positive with periodic acid–Schiff.⁴ Lymphocytes, plasma cells, and hemosiderin-laden macrophages are admixed within this pathologic architecture.^4,5

Visceral KS most commonly occurs in the oropharynx, respiratory tract, and gastrointestinal tract, and rarely is the initial presentation of disease. Classically, visceral KS is an aggressive, potentially life-threatening form of disease and has been found to have a much worse prognosis than cutaneous KS alone. Pulmonary involvement is the second most common site of extracutaneous KS and is known as the most severely life-threatening form of disease.¹ Interestingly, since the advent of HAART, the incidence of KS with involvement of the visceral organs has declined at a more dramatic rate than cutaneous KS alone.³ Therefore, although more aggressive in nature, KS with visceral features has become increasingly rare and should be largely preventable given advances in AIDS therapy. We present a case of advanced AIDS-related KS with pulmonary involvement that is rarely seen after the advent of HAART.

A 39-year-old man with HIV diagnosed 8 years prior presented with fever, chest pain, progressive dyspnea, and hemoptysis of 5 months’ duration. At the time, he was nonadherent to medications and had poor follow-up with primary care physicians. At presentation he was tachycardic (149 beats per minute), tachypneic (26 breaths per minute), and his oxygen saturation was 80% on room air. Physical examination of the skin revealed asymptomatic violaceous penile lesions that the patient reported had been present for the last 8 months (Figure 1). Pertinent laboratory values included an HIV-1 viral load of 480,135 copies/mL (reference range, <20 copies/mL) and CD4 count of 14 cells/mm³ (reference range, 480–1700 cells/mm³). A chest radiograph was obtained and revealed bibasilar opacities compatible with a pleural and/or parenchymal process. Bronchoscopy was then performed and revealed bloody secretions throughout the tracheobronchial tree.

Histologic examination of biopsies of the penile lesions revealed spindle cell proliferation with hemorrhage (Figure 2A) that stained positively for HHV-8 (Figure 2B), consistent with KS. Biopsies taken during bronchoscopy similarly revealed spindle cells with hemorrhage (Figure 3). The patient was diagnosed with AIDS-related KS with visceral involvement of the lung parenchyma and tracheobronchial tree. The patient was then admitted to the medical intensive care unit and intubated. Therapy with HAART and paclitaxel was initiated. After 7 days of poor response to therapy, the family opted for terminal extubation and comfort care measures. The patient died hours later.

It is evident that treatment of AIDS patients with HAART is not only first-line therapy for the disease but also the best preventative measure against development of KS. Management of KS also centers around the initiation of HAART if the patient is not already maintained on the proper therapy.⁸ In addition to HAART, treatment options for visceral KS include a variety of chemotherapeutic agents, including but not limited to the use of single-agent adriamycin, vinblastine, paclitaxel, and thalidomide, or combination therapies.

Although notable advances have been made in the management of AIDS patients, this case highlights the need for clinicians to be aware of the risk for KS in the context of immunocompromise. Specifically, patients with advanced AIDS who are not adherent to HAART or who have a poor response to therapy have an amplified risk for developing KS in general as well as an increased risk for developing more severe visceral KS. Maintenance of patients with HAART is shown to greatly reduce the risk for both cutaneous and visceral KS; therefore, patient adherence with therapy is of utmost importance in preventing the occurrence of this deadly disease and its complications. Appropriate follow-up should be made, ensuring that these patients at high risk are adherent to therapy and have proper access to medical care to allow for prevention and early identification of potential complications.

To the Editor:

Kaposi sarcoma (KS) is an angioproliferative tumor of endothelial origin associated with human herpesvirus 8 infection. It is one of the most prevalent opportunistic infections associated with AIDS and is considered an AIDS-defining illness. In the general population, the incidence of KS is 1 in 100,000 worldwide.¹ At the onset of the human immunodeficiency virus (HIV) epidemic in the early 1980s, 25% of individuals with AIDS were found to have KS at the time of AIDS diagnosis. Beginning in the mid-1980s and early 1990s with the introduction of highly active antiretroviral therapy (HAART), the incidence of KS declined to 2% to 4%,² likely secondary to restoration of immune response.³

The clinical course of KS ranges from benign to severe, involving both cutaneous and visceral forms of disease. Cutaneous KS is the most common form of disease and typically characterizes the initial presentation. It is classically described as violaceous patches, papules, or plaques that can become confluent, forming larger tumors over time. Biopsy of cutaneous lesions may vary based on the clinical morphology. The patch stage typically is characterized by abnormal proliferating vessels surrounding larger ectatic vessels.⁴ Vascular spaces are more jagged and lined by thin endothelial cells extending into the dermis, forming the classic promontory sign.⁵ In the plaque stage, the vascular infiltrate becomes more diffuse, involving the dermis and subcutis, and there is proliferation of spindle cells.⁴ In the nodular stage, spindle-shaped tumor cells form fascicles and vascular spaces become more dilated.^4,5 Advanced lesions are further associated with hyaline globules staining positive with periodic acid–Schiff.⁴ Lymphocytes, plasma cells, and hemosiderin-laden macrophages are admixed within this pathologic architecture.^4,5

Visceral KS most commonly occurs in the oropharynx, respiratory tract, and gastrointestinal tract, and rarely is the initial presentation of disease. Classically, visceral KS is an aggressive, potentially life-threatening form of disease and has been found to have a much worse prognosis than cutaneous KS alone. Pulmonary involvement is the second most common site of extracutaneous KS and is known as the most severely life-threatening form of disease.¹ Interestingly, since the advent of HAART, the incidence of KS with involvement of the visceral organs has declined at a more dramatic rate than cutaneous KS alone.³ Therefore, although more aggressive in nature, KS with visceral features has become increasingly rare and should be largely preventable given advances in AIDS therapy. We present a case of advanced AIDS-related KS with pulmonary involvement that is rarely seen after the advent of HAART.

A 39-year-old man with HIV diagnosed 8 years prior presented with fever, chest pain, progressive dyspnea, and hemoptysis of 5 months’ duration. At the time, he was nonadherent to medications and had poor follow-up with primary care physicians. At presentation he was tachycardic (149 beats per minute), tachypneic (26 breaths per minute), and his oxygen saturation was 80% on room air. Physical examination of the skin revealed asymptomatic violaceous penile lesions that the patient reported had been present for the last 8 months (Figure 1). Pertinent laboratory values included an HIV-1 viral load of 480,135 copies/mL (reference range, <20 copies/mL) and CD4 count of 14 cells/mm³ (reference range, 480–1700 cells/mm³). A chest radiograph was obtained and revealed bibasilar opacities compatible with a pleural and/or parenchymal process. Bronchoscopy was then performed and revealed bloody secretions throughout the tracheobronchial tree.

Histologic examination of biopsies of the penile lesions revealed spindle cell proliferation with hemorrhage (Figure 2A) that stained positively for HHV-8 (Figure 2B), consistent with KS. Biopsies taken during bronchoscopy similarly revealed spindle cells with hemorrhage (Figure 3). The patient was diagnosed with AIDS-related KS with visceral involvement of the lung parenchyma and tracheobronchial tree. The patient was then admitted to the medical intensive care unit and intubated. Therapy with HAART and paclitaxel was initiated. After 7 days of poor response to therapy, the family opted for terminal extubation and comfort care measures. The patient died hours later.

It is evident that treatment of AIDS patients with HAART is not only first-line therapy for the disease but also the best preventative measure against development of KS. Management of KS also centers around the initiation of HAART if the patient is not already maintained on the proper therapy.⁸ In addition to HAART, treatment options for visceral KS include a variety of chemotherapeutic agents, including but not limited to the use of single-agent adriamycin, vinblastine, paclitaxel, and thalidomide, or combination therapies.

Although notable advances have been made in the management of AIDS patients, this case highlights the need for clinicians to be aware of the risk for KS in the context of immunocompromise. Specifically, patients with advanced AIDS who are not adherent to HAART or who have a poor response to therapy have an amplified risk for developing KS in general as well as an increased risk for developing more severe visceral KS. Maintenance of patients with HAART is shown to greatly reduce the risk for both cutaneous and visceral KS; therefore, patient adherence with therapy is of utmost importance in preventing the occurrence of this deadly disease and its complications. Appropriate follow-up should be made, ensuring that these patients at high risk are adherent to therapy and have proper access to medical care to allow for prevention and early identification of potential complications.