Case Letter

To the Editor:

Relapsing polychondritis (RP) is a chronic, progressive, and episodic systemic inflammatory disease that primarily affects the cartilaginous structures of the ears and nose. Involvement of other proteoglycan-rich structures such as the joints, eyes, inner ears, blood vessels, heart, and kidneys also may be seen. Dermatologic manifestations occur in 35% to 50% of patients and may be the presenting sign in up to 12% of cases.¹ The most commonly reported dermatologic findings include oral aphthosis, erythema nodosum, and purpura with vasculitic changes. Less commonly reported associations include Sweet syndrome, pyoderma gangrenosum, panniculitis, erythema elevatum diutinum, erythema annulare centrifugum, and erythema multiforme.¹

A 43-year-old woman who was otherwise healthy developed new-onset tenderness and swelling of the left pinna while on vacation. She was treated with trimethoprim-sulfamethoxazole, clindamycin, and levofloxacin for presumed auricular cellulitis. The patient developed a fever; sore throat; and a progressive, pruritic, blistering rash on the face, torso, bilateral extremities, palms, and soles 1 day after completing the antibiotic course. After 5 days of unremitting symptoms despite oral, intramuscular, and topical steroids, the patient presented to the emergency department. Physical examination revealed diffuse, tender, erythematous to violaceous macules with varying degrees of coalescence on the chest, back, and extremities. Scattered flaccid bullae and erosions of the oral and genital mucosa also were seen. Laboratory analysis was notable only for a urinary tract infection with Klebsiella pneumoniae. A punch biopsy demonstrated full-thickness necrosis of the epidermis with subepidermal bullae and a mild to moderate lymphocytic infiltrate with rare eosinophils, consistent with a diagnosis of Stevens-Johnson syndrome (SJS). Because of the body surface area involved (20%) and the recent history of trimethoprim-sulfamethoxazole use, a diagnosis of SJS/toxic epidermal necrolysis (TEN) overlap syndrome was made. The patient was successfully treated with subcutaneous etanercept (50 mg), supportive care, and cephalexin for the urinary tract infection.

Approximately 5 weeks after discharge from the hospital, the patient was evaluated for new-onset pain and swelling of the right ear (Figure) in conjunction with recent tenderness and depression of the superior septal structure of the nose. A punch biopsy of the ear revealed mild perichondral inflammation without vasculitic changes and a superficial, deep perivascular, and periadnexal lymphoplasmacytic inflammatory infiltrate with scattered eosinophils. A diagnosis of RP was made, as the patient met Damiani and Levine’s² criteria with bilateral auricular inflammation, ocular inflammation, and nasal chondritis.

We report a unique case of SJS/TEN overlap syndrome occurring in a patient with RP.¹ Although the association may be coincidental, it is well known that patients with lupus erythematosus are predisposed to the development of SJS and TEN. Therefore, a shared underlying genetic predisposition or immune system hyperactivity secondary to active RP is a possible explanation for our patient’s unique presentation.

To the Editor:

Relapsing polychondritis (RP) is a chronic, progressive, and episodic systemic inflammatory disease that primarily affects the cartilaginous structures of the ears and nose. Involvement of other proteoglycan-rich structures such as the joints, eyes, inner ears, blood vessels, heart, and kidneys also may be seen. Dermatologic manifestations occur in 35% to 50% of patients and may be the presenting sign in up to 12% of cases.¹ The most commonly reported dermatologic findings include oral aphthosis, erythema nodosum, and purpura with vasculitic changes. Less commonly reported associations include Sweet syndrome, pyoderma gangrenosum, panniculitis, erythema elevatum diutinum, erythema annulare centrifugum, and erythema multiforme.¹

A 43-year-old woman who was otherwise healthy developed new-onset tenderness and swelling of the left pinna while on vacation. She was treated with trimethoprim-sulfamethoxazole, clindamycin, and levofloxacin for presumed auricular cellulitis. The patient developed a fever; sore throat; and a progressive, pruritic, blistering rash on the face, torso, bilateral extremities, palms, and soles 1 day after completing the antibiotic course. After 5 days of unremitting symptoms despite oral, intramuscular, and topical steroids, the patient presented to the emergency department. Physical examination revealed diffuse, tender, erythematous to violaceous macules with varying degrees of coalescence on the chest, back, and extremities. Scattered flaccid bullae and erosions of the oral and genital mucosa also were seen. Laboratory analysis was notable only for a urinary tract infection with Klebsiella pneumoniae. A punch biopsy demonstrated full-thickness necrosis of the epidermis with subepidermal bullae and a mild to moderate lymphocytic infiltrate with rare eosinophils, consistent with a diagnosis of Stevens-Johnson syndrome (SJS). Because of the body surface area involved (20%) and the recent history of trimethoprim-sulfamethoxazole use, a diagnosis of SJS/toxic epidermal necrolysis (TEN) overlap syndrome was made. The patient was successfully treated with subcutaneous etanercept (50 mg), supportive care, and cephalexin for the urinary tract infection.

Approximately 5 weeks after discharge from the hospital, the patient was evaluated for new-onset pain and swelling of the right ear (Figure) in conjunction with recent tenderness and depression of the superior septal structure of the nose. A punch biopsy of the ear revealed mild perichondral inflammation without vasculitic changes and a superficial, deep perivascular, and periadnexal lymphoplasmacytic inflammatory infiltrate with scattered eosinophils. A diagnosis of RP was made, as the patient met Damiani and Levine’s² criteria with bilateral auricular inflammation, ocular inflammation, and nasal chondritis.

We report a unique case of SJS/TEN overlap syndrome occurring in a patient with RP.¹ Although the association may be coincidental, it is well known that patients with lupus erythematosus are predisposed to the development of SJS and TEN. Therefore, a shared underlying genetic predisposition or immune system hyperactivity secondary to active RP is a possible explanation for our patient’s unique presentation.

To the Editor:

Relapsing polychondritis (RP) is a chronic, progressive, and episodic systemic inflammatory disease that primarily affects the cartilaginous structures of the ears and nose. Involvement of other proteoglycan-rich structures such as the joints, eyes, inner ears, blood vessels, heart, and kidneys also may be seen. Dermatologic manifestations occur in 35% to 50% of patients and may be the presenting sign in up to 12% of cases.¹ The most commonly reported dermatologic findings include oral aphthosis, erythema nodosum, and purpura with vasculitic changes. Less commonly reported associations include Sweet syndrome, pyoderma gangrenosum, panniculitis, erythema elevatum diutinum, erythema annulare centrifugum, and erythema multiforme.¹

A 43-year-old woman who was otherwise healthy developed new-onset tenderness and swelling of the left pinna while on vacation. She was treated with trimethoprim-sulfamethoxazole, clindamycin, and levofloxacin for presumed auricular cellulitis. The patient developed a fever; sore throat; and a progressive, pruritic, blistering rash on the face, torso, bilateral extremities, palms, and soles 1 day after completing the antibiotic course. After 5 days of unremitting symptoms despite oral, intramuscular, and topical steroids, the patient presented to the emergency department. Physical examination revealed diffuse, tender, erythematous to violaceous macules with varying degrees of coalescence on the chest, back, and extremities. Scattered flaccid bullae and erosions of the oral and genital mucosa also were seen. Laboratory analysis was notable only for a urinary tract infection with Klebsiella pneumoniae. A punch biopsy demonstrated full-thickness necrosis of the epidermis with subepidermal bullae and a mild to moderate lymphocytic infiltrate with rare eosinophils, consistent with a diagnosis of Stevens-Johnson syndrome (SJS). Because of the body surface area involved (20%) and the recent history of trimethoprim-sulfamethoxazole use, a diagnosis of SJS/toxic epidermal necrolysis (TEN) overlap syndrome was made. The patient was successfully treated with subcutaneous etanercept (50 mg), supportive care, and cephalexin for the urinary tract infection.

Approximately 5 weeks after discharge from the hospital, the patient was evaluated for new-onset pain and swelling of the right ear (Figure) in conjunction with recent tenderness and depression of the superior septal structure of the nose. A punch biopsy of the ear revealed mild perichondral inflammation without vasculitic changes and a superficial, deep perivascular, and periadnexal lymphoplasmacytic inflammatory infiltrate with scattered eosinophils. A diagnosis of RP was made, as the patient met Damiani and Levine’s² criteria with bilateral auricular inflammation, ocular inflammation, and nasal chondritis.

We report a unique case of SJS/TEN overlap syndrome occurring in a patient with RP.¹ Although the association may be coincidental, it is well known that patients with lupus erythematosus are predisposed to the development of SJS and TEN. Therefore, a shared underlying genetic predisposition or immune system hyperactivity secondary to active RP is a possible explanation for our patient’s unique presentation.

To the Editor:

Injectable fillers are an increasingly common means of achieving minimally invasive facial rejuvenation. In the hands of well-trained practitioners, these compounds typically are well tolerated, effective, and have a strong safety profile¹; however, there have been reports of complications, including vision loss,² orbital infarction,³ persistent inflammatory nodules,⁴ and infection.^4,5 Paraffin, a derivative of mineral oil, currently is used in cosmetic products and medical ointments.⁶ In the early 1900s, it often was injected into the body for various medical procedures, such as to create prosthetic testicles, to treat bladder incontinence, and eventually to correct facial contour defects.^7,8 Due to adverse effects, injection of paraffin oil was discontinued in the Western medical community around the time of World War I.⁷ Unfortunately, some patients continue to self-inject paraffin oil for cosmetic purposes today. We present a case of foreign-body granuloma formation mimicking periorbital cellulitis following self-injection of paraffin oil. Our patient developed serious periorbital sequelae that required surgical intervention to restore normal anatomic function.

A 60-year-old woman who was otherwise healthy presented to the emergency department with facial swelling and a rash of 2 weeks’ duration. She reported that she had purchased what she believed was a cosmetic product at a local flea market 2 weeks prior to presentation. Her purchase included needles and a syringe with verbal instructions for injection into the face. She was told the product was used to treat wrinkles and referred to the injectable material as “oil” when providing her history. She reported that she had injected the material into the bilateral lower eyelids, left lateral lip, and left lateral chin. Three days later, she developed tingling and itching with swelling and redness at the injection sites. The patient was evaluated by the emergency department team and was prescribed a 10-day course of clindamycin empirically for suspected facial cellulitis.

The patient returned to the emergency department 12 days later upon completion of the antibiotic course with worsening edema and erythema. Examination revealed indurated, erythematous, and edematous warm plaques on the face that were concentrated around the prior injection sites with substantial periorbital erythema and edema (Figure 1). A consultation with oculoplastic surgery was obtained. Mechanical ptosis of the right eyelid was noted. Visual acuity was 20/30 in both eyes with habitual correction. Intraocular pressure was soft to palpation, and the pupils were round and reactive with no evidence of a relative afferent pupillary defect. Extraocular motility was intact bilaterally. Examination of the conjunctiva and sclera revealed bilateral conjunctival injection with chemosis of the right eye. The remainder of the anterior and posterior segment examination was within normal limits bilaterally.

The tissue culture revealed normal skin flora. The biopsy results indicated a foreign-body reaction consistent with paraffin granuloma (Figures 2 and 3). Fite-Faraco, Grocott-Gomori methenamine-silver, and periodic acid–Schiff stains were all negative for infection. A diagnosis of foreign-body granuloma was established. Oral minocycline at a dosage of 100 mg twice daily was started, and the patient was discharged.

After 4 weeks of minocycline therapy, the patient showed no improvement and returned to the emergency department with worsening symptoms. She was readmitted and started on intravenous prednisone (1.5 mg/kg/d). Over the ensuing 5 days, the edema, erythema, conjunctival injection, and chemosis demonstrated notable improvement. She was subsequently discharged on an oral prednisone taper. Unfortunately, she did not respond to a trial of intralesional steroid injections to an area of granuloma formation on the left chin performed in the hospital before she was discharged.

In the ensuing months, she began to develop cicatricial ectropion of the right lower eyelid and mechanical ptosis of the right upper eyelid. Ten months after initial self-injection, staged surgical excision was initiated by an oculoplastic surgeon (I.V.) with the goal of debulking the periorbital region to correct the ectropion and mechanical ptosis. A transconjunctival approach was used to carefully excise the material while still maintaining the architecture of the lower eyelid. The ectropion was surgically corrected concurrently.

One month after excision, serial injections of 5-fluorouracil (5-FU) and triamcinolone acetonide 40 mg/mL were administered to the right lower eyelid and anterior orbit for 3 months. Fifteen weeks after the first surgery, a second surgery was performed to address residual medial right lower eyelid induration, right upper eyelid mechanical ptosis, and left orbital inflammation. During the postoperative period, serial monthly injections of 5-FU and triamcinolone acetonide were again performed beginning at the first postoperative month.

The surgical excisions resulted in notable improvement 3 months following excision (Figure 4). The patient noted improved ocular surface comfort with decreased foreign-body sensation and tearing. She also was pleased with the improved cosmetic outcome.

To the Editor:

Injectable fillers are an increasingly common means of achieving minimally invasive facial rejuvenation. In the hands of well-trained practitioners, these compounds typically are well tolerated, effective, and have a strong safety profile¹; however, there have been reports of complications, including vision loss,² orbital infarction,³ persistent inflammatory nodules,⁴ and infection.^4,5 Paraffin, a derivative of mineral oil, currently is used in cosmetic products and medical ointments.⁶ In the early 1900s, it often was injected into the body for various medical procedures, such as to create prosthetic testicles, to treat bladder incontinence, and eventually to correct facial contour defects.^7,8 Due to adverse effects, injection of paraffin oil was discontinued in the Western medical community around the time of World War I.⁷ Unfortunately, some patients continue to self-inject paraffin oil for cosmetic purposes today. We present a case of foreign-body granuloma formation mimicking periorbital cellulitis following self-injection of paraffin oil. Our patient developed serious periorbital sequelae that required surgical intervention to restore normal anatomic function.

A 60-year-old woman who was otherwise healthy presented to the emergency department with facial swelling and a rash of 2 weeks’ duration. She reported that she had purchased what she believed was a cosmetic product at a local flea market 2 weeks prior to presentation. Her purchase included needles and a syringe with verbal instructions for injection into the face. She was told the product was used to treat wrinkles and referred to the injectable material as “oil” when providing her history. She reported that she had injected the material into the bilateral lower eyelids, left lateral lip, and left lateral chin. Three days later, she developed tingling and itching with swelling and redness at the injection sites. The patient was evaluated by the emergency department team and was prescribed a 10-day course of clindamycin empirically for suspected facial cellulitis.

The patient returned to the emergency department 12 days later upon completion of the antibiotic course with worsening edema and erythema. Examination revealed indurated, erythematous, and edematous warm plaques on the face that were concentrated around the prior injection sites with substantial periorbital erythema and edema (Figure 1). A consultation with oculoplastic surgery was obtained. Mechanical ptosis of the right eyelid was noted. Visual acuity was 20/30 in both eyes with habitual correction. Intraocular pressure was soft to palpation, and the pupils were round and reactive with no evidence of a relative afferent pupillary defect. Extraocular motility was intact bilaterally. Examination of the conjunctiva and sclera revealed bilateral conjunctival injection with chemosis of the right eye. The remainder of the anterior and posterior segment examination was within normal limits bilaterally.

The tissue culture revealed normal skin flora. The biopsy results indicated a foreign-body reaction consistent with paraffin granuloma (Figures 2 and 3). Fite-Faraco, Grocott-Gomori methenamine-silver, and periodic acid–Schiff stains were all negative for infection. A diagnosis of foreign-body granuloma was established. Oral minocycline at a dosage of 100 mg twice daily was started, and the patient was discharged.

After 4 weeks of minocycline therapy, the patient showed no improvement and returned to the emergency department with worsening symptoms. She was readmitted and started on intravenous prednisone (1.5 mg/kg/d). Over the ensuing 5 days, the edema, erythema, conjunctival injection, and chemosis demonstrated notable improvement. She was subsequently discharged on an oral prednisone taper. Unfortunately, she did not respond to a trial of intralesional steroid injections to an area of granuloma formation on the left chin performed in the hospital before she was discharged.

In the ensuing months, she began to develop cicatricial ectropion of the right lower eyelid and mechanical ptosis of the right upper eyelid. Ten months after initial self-injection, staged surgical excision was initiated by an oculoplastic surgeon (I.V.) with the goal of debulking the periorbital region to correct the ectropion and mechanical ptosis. A transconjunctival approach was used to carefully excise the material while still maintaining the architecture of the lower eyelid. The ectropion was surgically corrected concurrently.

One month after excision, serial injections of 5-fluorouracil (5-FU) and triamcinolone acetonide 40 mg/mL were administered to the right lower eyelid and anterior orbit for 3 months. Fifteen weeks after the first surgery, a second surgery was performed to address residual medial right lower eyelid induration, right upper eyelid mechanical ptosis, and left orbital inflammation. During the postoperative period, serial monthly injections of 5-FU and triamcinolone acetonide were again performed beginning at the first postoperative month.

The surgical excisions resulted in notable improvement 3 months following excision (Figure 4). The patient noted improved ocular surface comfort with decreased foreign-body sensation and tearing. She also was pleased with the improved cosmetic outcome.

To the Editor:

Injectable fillers are an increasingly common means of achieving minimally invasive facial rejuvenation. In the hands of well-trained practitioners, these compounds typically are well tolerated, effective, and have a strong safety profile¹; however, there have been reports of complications, including vision loss,² orbital infarction,³ persistent inflammatory nodules,⁴ and infection.^4,5 Paraffin, a derivative of mineral oil, currently is used in cosmetic products and medical ointments.⁶ In the early 1900s, it often was injected into the body for various medical procedures, such as to create prosthetic testicles, to treat bladder incontinence, and eventually to correct facial contour defects.^7,8 Due to adverse effects, injection of paraffin oil was discontinued in the Western medical community around the time of World War I.⁷ Unfortunately, some patients continue to self-inject paraffin oil for cosmetic purposes today. We present a case of foreign-body granuloma formation mimicking periorbital cellulitis following self-injection of paraffin oil. Our patient developed serious periorbital sequelae that required surgical intervention to restore normal anatomic function.

A 60-year-old woman who was otherwise healthy presented to the emergency department with facial swelling and a rash of 2 weeks’ duration. She reported that she had purchased what she believed was a cosmetic product at a local flea market 2 weeks prior to presentation. Her purchase included needles and a syringe with verbal instructions for injection into the face. She was told the product was used to treat wrinkles and referred to the injectable material as “oil” when providing her history. She reported that she had injected the material into the bilateral lower eyelids, left lateral lip, and left lateral chin. Three days later, she developed tingling and itching with swelling and redness at the injection sites. The patient was evaluated by the emergency department team and was prescribed a 10-day course of clindamycin empirically for suspected facial cellulitis.

The patient returned to the emergency department 12 days later upon completion of the antibiotic course with worsening edema and erythema. Examination revealed indurated, erythematous, and edematous warm plaques on the face that were concentrated around the prior injection sites with substantial periorbital erythema and edema (Figure 1). A consultation with oculoplastic surgery was obtained. Mechanical ptosis of the right eyelid was noted. Visual acuity was 20/30 in both eyes with habitual correction. Intraocular pressure was soft to palpation, and the pupils were round and reactive with no evidence of a relative afferent pupillary defect. Extraocular motility was intact bilaterally. Examination of the conjunctiva and sclera revealed bilateral conjunctival injection with chemosis of the right eye. The remainder of the anterior and posterior segment examination was within normal limits bilaterally.

The tissue culture revealed normal skin flora. The biopsy results indicated a foreign-body reaction consistent with paraffin granuloma (Figures 2 and 3). Fite-Faraco, Grocott-Gomori methenamine-silver, and periodic acid–Schiff stains were all negative for infection. A diagnosis of foreign-body granuloma was established. Oral minocycline at a dosage of 100 mg twice daily was started, and the patient was discharged.

After 4 weeks of minocycline therapy, the patient showed no improvement and returned to the emergency department with worsening symptoms. She was readmitted and started on intravenous prednisone (1.5 mg/kg/d). Over the ensuing 5 days, the edema, erythema, conjunctival injection, and chemosis demonstrated notable improvement. She was subsequently discharged on an oral prednisone taper. Unfortunately, she did not respond to a trial of intralesional steroid injections to an area of granuloma formation on the left chin performed in the hospital before she was discharged.

In the ensuing months, she began to develop cicatricial ectropion of the right lower eyelid and mechanical ptosis of the right upper eyelid. Ten months after initial self-injection, staged surgical excision was initiated by an oculoplastic surgeon (I.V.) with the goal of debulking the periorbital region to correct the ectropion and mechanical ptosis. A transconjunctival approach was used to carefully excise the material while still maintaining the architecture of the lower eyelid. The ectropion was surgically corrected concurrently.

One month after excision, serial injections of 5-fluorouracil (5-FU) and triamcinolone acetonide 40 mg/mL were administered to the right lower eyelid and anterior orbit for 3 months. Fifteen weeks after the first surgery, a second surgery was performed to address residual medial right lower eyelid induration, right upper eyelid mechanical ptosis, and left orbital inflammation. During the postoperative period, serial monthly injections of 5-FU and triamcinolone acetonide were again performed beginning at the first postoperative month.

The surgical excisions resulted in notable improvement 3 months following excision (Figure 4). The patient noted improved ocular surface comfort with decreased foreign-body sensation and tearing. She also was pleased with the improved cosmetic outcome.

To the Editor:

Tylosis with esophageal cancer was first described by Howel-Evans et al¹ in 1958 in a family from Liverpool, England. The disease is inherited in an autosomal-dominant fashion with a mutation in the tylosis with esophageal cancer gene, TOC.² The keratoderma associated with this syndrome has been reported to be focal in nature, painful, and primarily involving the plantar surfaces.³ Palmar involvement has been reported to manifest as calluses in patients who use their hands for manual labor.⁴ Oral leukoplakia also has been described in this syndrome⁵; however, long-term follow-up in one family demonstrated a benign course.⁶ Herein, we describe a case of painful tylosis in a patient with Howel-Evans syndrome who was successfully treated with acitretin.

A 50-year-old man presented to clinic for evaluation of hyperkeratosis of the palms and soles that began when he was a teenager. He reported the soles of the feet often were painful, especially without shoes (Figure, A). He used many over-the-counter emollients and tried both prescription and nonprescription keratolytics. At presentation, he was mechanically paring down some of the thickness of the calluses to decrease the pain.

We report a case of Howel-Evans keratoderma successfully managed with acitretin. In patients with painful keratoderma that is interfering with QOL, low-dose acitretin can be used to diminish these symptoms.

To the Editor:

Tylosis with esophageal cancer was first described by Howel-Evans et al¹ in 1958 in a family from Liverpool, England. The disease is inherited in an autosomal-dominant fashion with a mutation in the tylosis with esophageal cancer gene, TOC.² The keratoderma associated with this syndrome has been reported to be focal in nature, painful, and primarily involving the plantar surfaces.³ Palmar involvement has been reported to manifest as calluses in patients who use their hands for manual labor.⁴ Oral leukoplakia also has been described in this syndrome⁵; however, long-term follow-up in one family demonstrated a benign course.⁶ Herein, we describe a case of painful tylosis in a patient with Howel-Evans syndrome who was successfully treated with acitretin.

A 50-year-old man presented to clinic for evaluation of hyperkeratosis of the palms and soles that began when he was a teenager. He reported the soles of the feet often were painful, especially without shoes (Figure, A). He used many over-the-counter emollients and tried both prescription and nonprescription keratolytics. At presentation, he was mechanically paring down some of the thickness of the calluses to decrease the pain.

We report a case of Howel-Evans keratoderma successfully managed with acitretin. In patients with painful keratoderma that is interfering with QOL, low-dose acitretin can be used to diminish these symptoms.

To the Editor:

Tylosis with esophageal cancer was first described by Howel-Evans et al¹ in 1958 in a family from Liverpool, England. The disease is inherited in an autosomal-dominant fashion with a mutation in the tylosis with esophageal cancer gene, TOC.² The keratoderma associated with this syndrome has been reported to be focal in nature, painful, and primarily involving the plantar surfaces.³ Palmar involvement has been reported to manifest as calluses in patients who use their hands for manual labor.⁴ Oral leukoplakia also has been described in this syndrome⁵; however, long-term follow-up in one family demonstrated a benign course.⁶ Herein, we describe a case of painful tylosis in a patient with Howel-Evans syndrome who was successfully treated with acitretin.

A 50-year-old man presented to clinic for evaluation of hyperkeratosis of the palms and soles that began when he was a teenager. He reported the soles of the feet often were painful, especially without shoes (Figure, A). He used many over-the-counter emollients and tried both prescription and nonprescription keratolytics. At presentation, he was mechanically paring down some of the thickness of the calluses to decrease the pain.

We report a case of Howel-Evans keratoderma successfully managed with acitretin. In patients with painful keratoderma that is interfering with QOL, low-dose acitretin can be used to diminish these symptoms.

To the Editor:

Cutaneous filariasis is a group of infectious diseases caused by more than 60 different nematode species and endemic to approximately 83 countries.^1,2 These infections are transmitted to humans by vectors such as mosquitoes, blackflies, biting midges, or Tabanid flies.¹ The blood meal taken by vectors allow microfilariae to enter the skin and develop into adult worms.^1-3 It is postulated that filarial infections were first described in 2000 bc by Egyptian statues demonstrating elephantiasis, or swollen limbs, caused by chronic infections.¹ Although there are numerous filarial nematode species that infect humans, each life cycle is similar. First, the arthropod vector transmits infective larvae through human skin during a blood meal. Then larvae migrate to host body parts where they mature into adults. Infective filariae require 1 to 2 weeks to form; arthropods may then have another blood meal and transmit the infection to another host.¹

Filarial parasites have been categorized into groups based on the site of adult worm stage habitat. The cutaneous group includes Loa loa, Onchocerca volvulus, Mansonella perstans, and Dipetalonema streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lastly, the body cavity group includes Mansonella ozzardi. Because humidity is required for survival of the infective larval stage, individuals from tropical countries in Africa, Central America, and South America most commonly are affected.¹ These diseases also are related to poor housing quality and inadequate sanitation.^1,3,4 Travel for business, medical missions, pleasure, or emigration has caused increased filarial infections globally. In fact, dermatologic disorders with infectious etiologies cause approximately 17% of travelers to seek medical attention.³

Dermatologic manifestations indicative of a potential cutaneous filarial infection include papules, nodules, excoriations with secondary xerosis, lichenification, skin pigment changes, and/or severe pruritus. However, individuals from filarial endemic regions may not demonstrate any clinical signs or symptoms, despite having microfilariae in their blood,¹ which enables the disease to propagate and poses a major public health concern. In fact, patients with chronic filarial infections are at increased risk for developing lymphedema, elephantiasis, or blindness, which are hypothesized to be the second largest cause of permanent disability worldwide.¹ Although rarely seen in US citizens, cutaneous filariasis should always be a diagnostic consideration in patients who present with a pruritic eruption and have a travel history to tropical countries. We report a case of cutaneous onchocerciasis in a US citizen who developed a pruritic eczematous eruption on the right upper arm following an arthropod assault while working in an Onchocerca endemic region approximately 1.5 years prior.

A 33-year-old woman presented to our outpatient dermatology clinic with the chief concern of a pruritic rash on the right arm (Figure 1). She revealed a history of travel to Peru, associated symptoms, prior diagnoses, and attempted treatment regimens. Over a 1.5-year period, the patient traveled for work-related reasons to Madre de Dios, Peru. During that time, the patient experienced 2 bouts of severe abdominal pain, nausea, and vomiting that she attributed to poor food and water quality. She did not immediately seek medical attention. She also developed skin manifestations that began as a pruritic and irritating pinpoint-sized red papule on the right eyelid, possibly a site of an arthropod assault. She then experienced episodic eyelash loss (Figure 2) and subsequent vision changes, including blurry vision, halos around lights, and dimming around the periphery. When the patient developed circular, pink, pruritic plaques on the right upper extremity, she sought medical attention in Lima, Peru. She was diagnosed with tinea corporis and prescribed an oral antibiotic and topical antifungal.

A few days after the treatment for the blastocystis, the gastrointestinal tract symptoms improved, but dermatologic, ocular, pulmonary, and cardiac symptoms persisted. She also began experiencing night sweats and hot flashes. In between visits to the primary care physician, she sought medical attention at an urgent care clinic for worsening pulmonary and cardiac symptoms. At that time, results of a chest radiograph were normal.

The primary care physician referred her to infectious disease and dermatology for further evaluation within a few weeks of returning to the United States. Upon presentation to dermatology, the patient described a waxing and waning nature to the rash on the arm with associated intermittent pain. Physical examination revealed several erythematous patches on the triceps and a 1-cm subcutaneous nodule on the right elbow with overlying skin discoloration. The patient stated that she first noticed the inflamed painful nodule when she returned to the United States. Since its discovery, the nodule increased in size and became firm. The patient also described occasional limited range of motion of the right arm due to the discomfort of the rash and inflamed nodule. Interestingly, the patient’s partner who accompanied her to Peru also developed a similar pruritic rash on the chest. He was evaluated by dermatology and infectious disease; however, biopsies of his rash performed at a different practice revealed nonspecific results. Due to her partner’s inconclusive results, our patient initially refused a biopsy; however, she returned to the office after 1 week with worsening symptoms, and a 4-mm punch biopsy of the right arm was obtained in addition to rapid plasma reagin and QuantiFERON-TB Gold test.

Based on the patient’s travel history, clinical course, and physical examination, the clinical differential diagnosis included nummular dermatitis, panniculitis/nodular vasculitis, tinea corporis, secondary syphilis, pinta, tuberculosis, or cutaneous filariasis. Rapid plasma reagin and QuantiFERON-TB Gold test results were negative, and a periodic acid–Schiff stain of the biopsy was negative for fungal elements. Dermatopathology revealed intradermal filarial nematodes of 120 to 150 µm in diameter and 1-to 2-mm cuticles eliciting a predominantly superficial and deep lymphohistiocytic reaction (Figure 3). The histopathologic differential diagnosis based on the diameter of the nematode included M perstans, W bancrofti, and O volvulus. Clinical correlation was highly recommended to obtain a final diagnosis and management plan. A portion of the biopsy was sent to the Centers for Disease Control and Prevention, which confirmed the presence of a filarial nematode consistent with a zoonotic Brugia but also with zoonotic Onchocerca as a possible differential. Therefore, considering the history, clinical course, and histopathologic analysis, the final diagnosis of cutaneous onchocerciasis was made.

Onchocerciasis is common in individuals who live or work in equatorial Africa, Central America, and South America. The disease process has dermatologic, ocular, and other systemic manifestations if the infection continues long-term without treatment.^2,5 Although rare, this infection has been observed in US citizens who have traveled to filarial endemic regions for a period of time ranging from 2 weeks to 39 years.^2,6,7

Blackflies (genus Simulium), the intermediate host of O volvulus, breed in areas close to freely flowing water. The blackfly bites a human host, and within 7 days the microfilariae undergo 2 molts to reach the infective stage. The larvae remain in the dermis and subcutaneous tissue for 2 additional molts until they develop into adult worms. Then, adult worms may become encapsulated, eliciting and forming subcutaneous nodules, also known as onchocercomas.^2,3

A fertilized female in the subcutaneous tissue releases microfilariae that may remain in the skin or travel to the eyes of the host.³ The host may demonstrate signs of infection within 3 to 15 months.² Most commonly, patients report localized or generalized pruritus, and one extremity develops swelling, papules, lymphadenopathy, and alterations of skin pigment (hypopigmentation or hyperpigmentation).^5-8 Our patient developed a pruritic eczematous eruption that only affected her right arm with an inflamed firm nodule overlying the elbow, a suspected onchocercoma. Onchocercomas are the direct result of adult worms coiled in the dermis, subcutaneous tissue, and deep fascia. These commonly are found in close proximity to bony prominences with the specific location pending the geographic area of infection.⁸ For example, onchocercomas more commonly are found over bony prominences in the head and upper body region in patients who acquired the disease from Central or South America, whereas individuals infected in Africa more commonly develop onchocercomas near the femoral, coccyx, or sacral regions.²

The immune response mounted by the infected host is responsible for the ocular signs and symptoms.² Specifically, the inflammatory reaction may impact the patient’s cornea, anterior uveal tract, chorioretinal zone, or optic nerve. In fact, onchocerciasis, or river blindness, is the leading cause of blindness in the world.² The host immune response also is responsible for the dermatologic manifestations of this disease. In addition to the dermatologic manifestations already mentioned, others include epidermal atrophy, ulcerations, femoral or inguinal lymphadenitis, lymphedema, and/or general wasting in more severe long-standing infections. Additionally, patients may experience systemic signs resulting from an underlying O volvulus infection.⁸ Our patient demonstrated a subjectively remarkable systemic response manifested by shortness of breath, dyspnea, cough, and palpitations, likely the result of her existing filarial infection.

Diagnosis of onchocerciasis is made by identification of microfilariae or adult worms in skin snips or punch biopsies. Histopathologic analysis of onchocerciasis has been described as several adult worms in the subcutaneous tissue surrounded by a granulomatous, fibrotic, calcified, or sometimes ossified inflammatory reaction.⁸ Microfilariae may migrate to the upper dermis and typically are surrounded by lymphocytes, histiocytes, plasma cells, and eosinophils with an absence of neutrophils,^5,8 which directly causes the overlying epidermis to undergo reactive changes. Measurement of filarial nematodes often helps differentiate species. For example, O volvulus typically measures 230 to 500 mm in length for females and 16 to 42 mm in length for males.⁸ The thickness of cuticles typically measures 4 to 8 µm for females and 3 to 5 µm for males. Microfilariae of O volvulus also have been identified in patient’s sputum, urine, blood, and spinal fluid.⁸ An alternative diagnostic method described by Stingl et al⁹ is a diethylcarbamazine (DEC) patch test that was 92% accurate in onchocerciasis cases diagnosed by skin snip analysis.⁹ Therefore, this test may be a practical alternative when skin specimens are inconclusive.

Management of onchocerciasis should include excision of subcutaneous nodules to remove adult worms. In the past, DEC with suramin was prescribed and kills both microfilariae and adult worms.⁸ However, DEC may induce pruritus, chorioretinal damage, and optic neuritis and suramin is nephrotoxic.² Therefore, oral ivermectin (0.15–0.20 mg/kg one-time dose, may be repeated in 3–12 months) is supported to be a less harmful option. Patients treated with ivermectin have a decreased risk for transmitting infection to the blackfly vector for up to 6 months after treatment, and it is a more effective microfilaricidal agent than DEC.^2,3 Oral doxycycline (100 mg/d for 6 weeks) commonly is added as adjuvant therapy because it kills Wolbachia species, a bacterium that is needed for O volvulus reproduction.³

Although rare in the United States, cutaneous filariasis has become a prevalent public health concern, especially in tropical countries. Individuals with chronic cutaneous filarial infections are at increased risk for debilitating complications that negatively affect their quality of life and productivity. Although the World Health Organization has attempted to eradicate cutaneous filarial infections by mass drug administration, transmission of these diseases remains a challenge. Further research on treatment and methods to prevent transmission by controlling arthropod vectors is required to avoid short-term and long-term health consequences caused by cutaneous filariasis.

Parasitic infections should always be a diagnostic consideration in individuals who present with a pruritic eruption and a history of travel to foreign countries located in Africa, Central America, and South America. Dermatologists in the United States should increase familiarity with these infections because of increased travel, economic globalization, and the impact of global climate change on the geographic distribution of vector arthropods. To control these infections, research efforts should focus on improved sanitation; drug treatment; transmission prevention; and improved education of their clinical manifestations, especially mucocutaneous signs.

To the Editor:

Cutaneous filariasis is a group of infectious diseases caused by more than 60 different nematode species and endemic to approximately 83 countries.^1,2 These infections are transmitted to humans by vectors such as mosquitoes, blackflies, biting midges, or Tabanid flies.¹ The blood meal taken by vectors allow microfilariae to enter the skin and develop into adult worms.^1-3 It is postulated that filarial infections were first described in 2000 bc by Egyptian statues demonstrating elephantiasis, or swollen limbs, caused by chronic infections.¹ Although there are numerous filarial nematode species that infect humans, each life cycle is similar. First, the arthropod vector transmits infective larvae through human skin during a blood meal. Then larvae migrate to host body parts where they mature into adults. Infective filariae require 1 to 2 weeks to form; arthropods may then have another blood meal and transmit the infection to another host.¹

Filarial parasites have been categorized into groups based on the site of adult worm stage habitat. The cutaneous group includes Loa loa, Onchocerca volvulus, Mansonella perstans, and Dipetalonema streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lastly, the body cavity group includes Mansonella ozzardi. Because humidity is required for survival of the infective larval stage, individuals from tropical countries in Africa, Central America, and South America most commonly are affected.¹ These diseases also are related to poor housing quality and inadequate sanitation.^1,3,4 Travel for business, medical missions, pleasure, or emigration has caused increased filarial infections globally. In fact, dermatologic disorders with infectious etiologies cause approximately 17% of travelers to seek medical attention.³

Dermatologic manifestations indicative of a potential cutaneous filarial infection include papules, nodules, excoriations with secondary xerosis, lichenification, skin pigment changes, and/or severe pruritus. However, individuals from filarial endemic regions may not demonstrate any clinical signs or symptoms, despite having microfilariae in their blood,¹ which enables the disease to propagate and poses a major public health concern. In fact, patients with chronic filarial infections are at increased risk for developing lymphedema, elephantiasis, or blindness, which are hypothesized to be the second largest cause of permanent disability worldwide.¹ Although rarely seen in US citizens, cutaneous filariasis should always be a diagnostic consideration in patients who present with a pruritic eruption and have a travel history to tropical countries. We report a case of cutaneous onchocerciasis in a US citizen who developed a pruritic eczematous eruption on the right upper arm following an arthropod assault while working in an Onchocerca endemic region approximately 1.5 years prior.

A 33-year-old woman presented to our outpatient dermatology clinic with the chief concern of a pruritic rash on the right arm (Figure 1). She revealed a history of travel to Peru, associated symptoms, prior diagnoses, and attempted treatment regimens. Over a 1.5-year period, the patient traveled for work-related reasons to Madre de Dios, Peru. During that time, the patient experienced 2 bouts of severe abdominal pain, nausea, and vomiting that she attributed to poor food and water quality. She did not immediately seek medical attention. She also developed skin manifestations that began as a pruritic and irritating pinpoint-sized red papule on the right eyelid, possibly a site of an arthropod assault. She then experienced episodic eyelash loss (Figure 2) and subsequent vision changes, including blurry vision, halos around lights, and dimming around the periphery. When the patient developed circular, pink, pruritic plaques on the right upper extremity, she sought medical attention in Lima, Peru. She was diagnosed with tinea corporis and prescribed an oral antibiotic and topical antifungal.

A few days after the treatment for the blastocystis, the gastrointestinal tract symptoms improved, but dermatologic, ocular, pulmonary, and cardiac symptoms persisted. She also began experiencing night sweats and hot flashes. In between visits to the primary care physician, she sought medical attention at an urgent care clinic for worsening pulmonary and cardiac symptoms. At that time, results of a chest radiograph were normal.

The primary care physician referred her to infectious disease and dermatology for further evaluation within a few weeks of returning to the United States. Upon presentation to dermatology, the patient described a waxing and waning nature to the rash on the arm with associated intermittent pain. Physical examination revealed several erythematous patches on the triceps and a 1-cm subcutaneous nodule on the right elbow with overlying skin discoloration. The patient stated that she first noticed the inflamed painful nodule when she returned to the United States. Since its discovery, the nodule increased in size and became firm. The patient also described occasional limited range of motion of the right arm due to the discomfort of the rash and inflamed nodule. Interestingly, the patient’s partner who accompanied her to Peru also developed a similar pruritic rash on the chest. He was evaluated by dermatology and infectious disease; however, biopsies of his rash performed at a different practice revealed nonspecific results. Due to her partner’s inconclusive results, our patient initially refused a biopsy; however, she returned to the office after 1 week with worsening symptoms, and a 4-mm punch biopsy of the right arm was obtained in addition to rapid plasma reagin and QuantiFERON-TB Gold test.

Based on the patient’s travel history, clinical course, and physical examination, the clinical differential diagnosis included nummular dermatitis, panniculitis/nodular vasculitis, tinea corporis, secondary syphilis, pinta, tuberculosis, or cutaneous filariasis. Rapid plasma reagin and QuantiFERON-TB Gold test results were negative, and a periodic acid–Schiff stain of the biopsy was negative for fungal elements. Dermatopathology revealed intradermal filarial nematodes of 120 to 150 µm in diameter and 1-to 2-mm cuticles eliciting a predominantly superficial and deep lymphohistiocytic reaction (Figure 3). The histopathologic differential diagnosis based on the diameter of the nematode included M perstans, W bancrofti, and O volvulus. Clinical correlation was highly recommended to obtain a final diagnosis and management plan. A portion of the biopsy was sent to the Centers for Disease Control and Prevention, which confirmed the presence of a filarial nematode consistent with a zoonotic Brugia but also with zoonotic Onchocerca as a possible differential. Therefore, considering the history, clinical course, and histopathologic analysis, the final diagnosis of cutaneous onchocerciasis was made.

Onchocerciasis is common in individuals who live or work in equatorial Africa, Central America, and South America. The disease process has dermatologic, ocular, and other systemic manifestations if the infection continues long-term without treatment.^2,5 Although rare, this infection has been observed in US citizens who have traveled to filarial endemic regions for a period of time ranging from 2 weeks to 39 years.^2,6,7

Blackflies (genus Simulium), the intermediate host of O volvulus, breed in areas close to freely flowing water. The blackfly bites a human host, and within 7 days the microfilariae undergo 2 molts to reach the infective stage. The larvae remain in the dermis and subcutaneous tissue for 2 additional molts until they develop into adult worms. Then, adult worms may become encapsulated, eliciting and forming subcutaneous nodules, also known as onchocercomas.^2,3

A fertilized female in the subcutaneous tissue releases microfilariae that may remain in the skin or travel to the eyes of the host.³ The host may demonstrate signs of infection within 3 to 15 months.² Most commonly, patients report localized or generalized pruritus, and one extremity develops swelling, papules, lymphadenopathy, and alterations of skin pigment (hypopigmentation or hyperpigmentation).^5-8 Our patient developed a pruritic eczematous eruption that only affected her right arm with an inflamed firm nodule overlying the elbow, a suspected onchocercoma. Onchocercomas are the direct result of adult worms coiled in the dermis, subcutaneous tissue, and deep fascia. These commonly are found in close proximity to bony prominences with the specific location pending the geographic area of infection.⁸ For example, onchocercomas more commonly are found over bony prominences in the head and upper body region in patients who acquired the disease from Central or South America, whereas individuals infected in Africa more commonly develop onchocercomas near the femoral, coccyx, or sacral regions.²

The immune response mounted by the infected host is responsible for the ocular signs and symptoms.² Specifically, the inflammatory reaction may impact the patient’s cornea, anterior uveal tract, chorioretinal zone, or optic nerve. In fact, onchocerciasis, or river blindness, is the leading cause of blindness in the world.² The host immune response also is responsible for the dermatologic manifestations of this disease. In addition to the dermatologic manifestations already mentioned, others include epidermal atrophy, ulcerations, femoral or inguinal lymphadenitis, lymphedema, and/or general wasting in more severe long-standing infections. Additionally, patients may experience systemic signs resulting from an underlying O volvulus infection.⁸ Our patient demonstrated a subjectively remarkable systemic response manifested by shortness of breath, dyspnea, cough, and palpitations, likely the result of her existing filarial infection.

Diagnosis of onchocerciasis is made by identification of microfilariae or adult worms in skin snips or punch biopsies. Histopathologic analysis of onchocerciasis has been described as several adult worms in the subcutaneous tissue surrounded by a granulomatous, fibrotic, calcified, or sometimes ossified inflammatory reaction.⁸ Microfilariae may migrate to the upper dermis and typically are surrounded by lymphocytes, histiocytes, plasma cells, and eosinophils with an absence of neutrophils,^5,8 which directly causes the overlying epidermis to undergo reactive changes. Measurement of filarial nematodes often helps differentiate species. For example, O volvulus typically measures 230 to 500 mm in length for females and 16 to 42 mm in length for males.⁸ The thickness of cuticles typically measures 4 to 8 µm for females and 3 to 5 µm for males. Microfilariae of O volvulus also have been identified in patient’s sputum, urine, blood, and spinal fluid.⁸ An alternative diagnostic method described by Stingl et al⁹ is a diethylcarbamazine (DEC) patch test that was 92% accurate in onchocerciasis cases diagnosed by skin snip analysis.⁹ Therefore, this test may be a practical alternative when skin specimens are inconclusive.

Management of onchocerciasis should include excision of subcutaneous nodules to remove adult worms. In the past, DEC with suramin was prescribed and kills both microfilariae and adult worms.⁸ However, DEC may induce pruritus, chorioretinal damage, and optic neuritis and suramin is nephrotoxic.² Therefore, oral ivermectin (0.15–0.20 mg/kg one-time dose, may be repeated in 3–12 months) is supported to be a less harmful option. Patients treated with ivermectin have a decreased risk for transmitting infection to the blackfly vector for up to 6 months after treatment, and it is a more effective microfilaricidal agent than DEC.^2,3 Oral doxycycline (100 mg/d for 6 weeks) commonly is added as adjuvant therapy because it kills Wolbachia species, a bacterium that is needed for O volvulus reproduction.³

Although rare in the United States, cutaneous filariasis has become a prevalent public health concern, especially in tropical countries. Individuals with chronic cutaneous filarial infections are at increased risk for debilitating complications that negatively affect their quality of life and productivity. Although the World Health Organization has attempted to eradicate cutaneous filarial infections by mass drug administration, transmission of these diseases remains a challenge. Further research on treatment and methods to prevent transmission by controlling arthropod vectors is required to avoid short-term and long-term health consequences caused by cutaneous filariasis.

Parasitic infections should always be a diagnostic consideration in individuals who present with a pruritic eruption and a history of travel to foreign countries located in Africa, Central America, and South America. Dermatologists in the United States should increase familiarity with these infections because of increased travel, economic globalization, and the impact of global climate change on the geographic distribution of vector arthropods. To control these infections, research efforts should focus on improved sanitation; drug treatment; transmission prevention; and improved education of their clinical manifestations, especially mucocutaneous signs.

To the Editor:

Cutaneous filariasis is a group of infectious diseases caused by more than 60 different nematode species and endemic to approximately 83 countries.^1,2 These infections are transmitted to humans by vectors such as mosquitoes, blackflies, biting midges, or Tabanid flies.¹ The blood meal taken by vectors allow microfilariae to enter the skin and develop into adult worms.^1-3 It is postulated that filarial infections were first described in 2000 bc by Egyptian statues demonstrating elephantiasis, or swollen limbs, caused by chronic infections.¹ Although there are numerous filarial nematode species that infect humans, each life cycle is similar. First, the arthropod vector transmits infective larvae through human skin during a blood meal. Then larvae migrate to host body parts where they mature into adults. Infective filariae require 1 to 2 weeks to form; arthropods may then have another blood meal and transmit the infection to another host.¹

Filarial parasites have been categorized into groups based on the site of adult worm stage habitat. The cutaneous group includes Loa loa, Onchocerca volvulus, Mansonella perstans, and Dipetalonema streptocerca. The lymphatic group includes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Lastly, the body cavity group includes Mansonella ozzardi. Because humidity is required for survival of the infective larval stage, individuals from tropical countries in Africa, Central America, and South America most commonly are affected.¹ These diseases also are related to poor housing quality and inadequate sanitation.^1,3,4 Travel for business, medical missions, pleasure, or emigration has caused increased filarial infections globally. In fact, dermatologic disorders with infectious etiologies cause approximately 17% of travelers to seek medical attention.³

Dermatologic manifestations indicative of a potential cutaneous filarial infection include papules, nodules, excoriations with secondary xerosis, lichenification, skin pigment changes, and/or severe pruritus. However, individuals from filarial endemic regions may not demonstrate any clinical signs or symptoms, despite having microfilariae in their blood,¹ which enables the disease to propagate and poses a major public health concern. In fact, patients with chronic filarial infections are at increased risk for developing lymphedema, elephantiasis, or blindness, which are hypothesized to be the second largest cause of permanent disability worldwide.¹ Although rarely seen in US citizens, cutaneous filariasis should always be a diagnostic consideration in patients who present with a pruritic eruption and have a travel history to tropical countries. We report a case of cutaneous onchocerciasis in a US citizen who developed a pruritic eczematous eruption on the right upper arm following an arthropod assault while working in an Onchocerca endemic region approximately 1.5 years prior.

A 33-year-old woman presented to our outpatient dermatology clinic with the chief concern of a pruritic rash on the right arm (Figure 1). She revealed a history of travel to Peru, associated symptoms, prior diagnoses, and attempted treatment regimens. Over a 1.5-year period, the patient traveled for work-related reasons to Madre de Dios, Peru. During that time, the patient experienced 2 bouts of severe abdominal pain, nausea, and vomiting that she attributed to poor food and water quality. She did not immediately seek medical attention. She also developed skin manifestations that began as a pruritic and irritating pinpoint-sized red papule on the right eyelid, possibly a site of an arthropod assault. She then experienced episodic eyelash loss (Figure 2) and subsequent vision changes, including blurry vision, halos around lights, and dimming around the periphery. When the patient developed circular, pink, pruritic plaques on the right upper extremity, she sought medical attention in Lima, Peru. She was diagnosed with tinea corporis and prescribed an oral antibiotic and topical antifungal.

A few days after the treatment for the blastocystis, the gastrointestinal tract symptoms improved, but dermatologic, ocular, pulmonary, and cardiac symptoms persisted. She also began experiencing night sweats and hot flashes. In between visits to the primary care physician, she sought medical attention at an urgent care clinic for worsening pulmonary and cardiac symptoms. At that time, results of a chest radiograph were normal.

The primary care physician referred her to infectious disease and dermatology for further evaluation within a few weeks of returning to the United States. Upon presentation to dermatology, the patient described a waxing and waning nature to the rash on the arm with associated intermittent pain. Physical examination revealed several erythematous patches on the triceps and a 1-cm subcutaneous nodule on the right elbow with overlying skin discoloration. The patient stated that she first noticed the inflamed painful nodule when she returned to the United States. Since its discovery, the nodule increased in size and became firm. The patient also described occasional limited range of motion of the right arm due to the discomfort of the rash and inflamed nodule. Interestingly, the patient’s partner who accompanied her to Peru also developed a similar pruritic rash on the chest. He was evaluated by dermatology and infectious disease; however, biopsies of his rash performed at a different practice revealed nonspecific results. Due to her partner’s inconclusive results, our patient initially refused a biopsy; however, she returned to the office after 1 week with worsening symptoms, and a 4-mm punch biopsy of the right arm was obtained in addition to rapid plasma reagin and QuantiFERON-TB Gold test.

Based on the patient’s travel history, clinical course, and physical examination, the clinical differential diagnosis included nummular dermatitis, panniculitis/nodular vasculitis, tinea corporis, secondary syphilis, pinta, tuberculosis, or cutaneous filariasis. Rapid plasma reagin and QuantiFERON-TB Gold test results were negative, and a periodic acid–Schiff stain of the biopsy was negative for fungal elements. Dermatopathology revealed intradermal filarial nematodes of 120 to 150 µm in diameter and 1-to 2-mm cuticles eliciting a predominantly superficial and deep lymphohistiocytic reaction (Figure 3). The histopathologic differential diagnosis based on the diameter of the nematode included M perstans, W bancrofti, and O volvulus. Clinical correlation was highly recommended to obtain a final diagnosis and management plan. A portion of the biopsy was sent to the Centers for Disease Control and Prevention, which confirmed the presence of a filarial nematode consistent with a zoonotic Brugia but also with zoonotic Onchocerca as a possible differential. Therefore, considering the history, clinical course, and histopathologic analysis, the final diagnosis of cutaneous onchocerciasis was made.

Onchocerciasis is common in individuals who live or work in equatorial Africa, Central America, and South America. The disease process has dermatologic, ocular, and other systemic manifestations if the infection continues long-term without treatment.^2,5 Although rare, this infection has been observed in US citizens who have traveled to filarial endemic regions for a period of time ranging from 2 weeks to 39 years.^2,6,7

Blackflies (genus Simulium), the intermediate host of O volvulus, breed in areas close to freely flowing water. The blackfly bites a human host, and within 7 days the microfilariae undergo 2 molts to reach the infective stage. The larvae remain in the dermis and subcutaneous tissue for 2 additional molts until they develop into adult worms. Then, adult worms may become encapsulated, eliciting and forming subcutaneous nodules, also known as onchocercomas.^2,3

A fertilized female in the subcutaneous tissue releases microfilariae that may remain in the skin or travel to the eyes of the host.³ The host may demonstrate signs of infection within 3 to 15 months.² Most commonly, patients report localized or generalized pruritus, and one extremity develops swelling, papules, lymphadenopathy, and alterations of skin pigment (hypopigmentation or hyperpigmentation).^5-8 Our patient developed a pruritic eczematous eruption that only affected her right arm with an inflamed firm nodule overlying the elbow, a suspected onchocercoma. Onchocercomas are the direct result of adult worms coiled in the dermis, subcutaneous tissue, and deep fascia. These commonly are found in close proximity to bony prominences with the specific location pending the geographic area of infection.⁸ For example, onchocercomas more commonly are found over bony prominences in the head and upper body region in patients who acquired the disease from Central or South America, whereas individuals infected in Africa more commonly develop onchocercomas near the femoral, coccyx, or sacral regions.²

The immune response mounted by the infected host is responsible for the ocular signs and symptoms.² Specifically, the inflammatory reaction may impact the patient’s cornea, anterior uveal tract, chorioretinal zone, or optic nerve. In fact, onchocerciasis, or river blindness, is the leading cause of blindness in the world.² The host immune response also is responsible for the dermatologic manifestations of this disease. In addition to the dermatologic manifestations already mentioned, others include epidermal atrophy, ulcerations, femoral or inguinal lymphadenitis, lymphedema, and/or general wasting in more severe long-standing infections. Additionally, patients may experience systemic signs resulting from an underlying O volvulus infection.⁸ Our patient demonstrated a subjectively remarkable systemic response manifested by shortness of breath, dyspnea, cough, and palpitations, likely the result of her existing filarial infection.

Diagnosis of onchocerciasis is made by identification of microfilariae or adult worms in skin snips or punch biopsies. Histopathologic analysis of onchocerciasis has been described as several adult worms in the subcutaneous tissue surrounded by a granulomatous, fibrotic, calcified, or sometimes ossified inflammatory reaction.⁸ Microfilariae may migrate to the upper dermis and typically are surrounded by lymphocytes, histiocytes, plasma cells, and eosinophils with an absence of neutrophils,^5,8 which directly causes the overlying epidermis to undergo reactive changes. Measurement of filarial nematodes often helps differentiate species. For example, O volvulus typically measures 230 to 500 mm in length for females and 16 to 42 mm in length for males.⁸ The thickness of cuticles typically measures 4 to 8 µm for females and 3 to 5 µm for males. Microfilariae of O volvulus also have been identified in patient’s sputum, urine, blood, and spinal fluid.⁸ An alternative diagnostic method described by Stingl et al⁹ is a diethylcarbamazine (DEC) patch test that was 92% accurate in onchocerciasis cases diagnosed by skin snip analysis.⁹ Therefore, this test may be a practical alternative when skin specimens are inconclusive.

Management of onchocerciasis should include excision of subcutaneous nodules to remove adult worms. In the past, DEC with suramin was prescribed and kills both microfilariae and adult worms.⁸ However, DEC may induce pruritus, chorioretinal damage, and optic neuritis and suramin is nephrotoxic.² Therefore, oral ivermectin (0.15–0.20 mg/kg one-time dose, may be repeated in 3–12 months) is supported to be a less harmful option. Patients treated with ivermectin have a decreased risk for transmitting infection to the blackfly vector for up to 6 months after treatment, and it is a more effective microfilaricidal agent than DEC.^2,3 Oral doxycycline (100 mg/d for 6 weeks) commonly is added as adjuvant therapy because it kills Wolbachia species, a bacterium that is needed for O volvulus reproduction.³

Although rare in the United States, cutaneous filariasis has become a prevalent public health concern, especially in tropical countries. Individuals with chronic cutaneous filarial infections are at increased risk for debilitating complications that negatively affect their quality of life and productivity. Although the World Health Organization has attempted to eradicate cutaneous filarial infections by mass drug administration, transmission of these diseases remains a challenge. Further research on treatment and methods to prevent transmission by controlling arthropod vectors is required to avoid short-term and long-term health consequences caused by cutaneous filariasis.

Parasitic infections should always be a diagnostic consideration in individuals who present with a pruritic eruption and a history of travel to foreign countries located in Africa, Central America, and South America. Dermatologists in the United States should increase familiarity with these infections because of increased travel, economic globalization, and the impact of global climate change on the geographic distribution of vector arthropods. To control these infections, research efforts should focus on improved sanitation; drug treatment; transmission prevention; and improved education of their clinical manifestations, especially mucocutaneous signs.

To the Editor:

Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is an autoimmune mucocutaneous blistering disease that typically occurs secondary to a lymphoproliferative disorder. Paraneoplastic pemphigus is characterized by severe erosive stomatitis, polymorphous skin lesions, and potential bronchiolitis obliterans that can mimic a wide array of conditions. The exact pathogenesis is unknown but is thought to be due to a combination of humoral and cell-mediated immunity. The condition usually confers a poor prognosis, with morbidity from 38% to upwards of 90%.¹

A 47-year-old man developed prominent pink to dusky, ill-defined, targetoid, coalescing papules over the back; violaceous macules over the palms and soles; and numerous crusted oral erosions while hospitalized for an infection. He had a history of stage IVB follicular lymphoma (double-hit type immunoglobulin heavy chain/BCL2 fusion and rearrangement of BCL6) complicated by extensive erosive skin lesions and multiple lines of infections. The clinical differential diagnosis included Stevens-Johnson syndrome vs erythema multiforme (EM) major secondary to administration of oxacillin vs PNP. Herpes simplex virus polymerase chain reaction and Mycoplasma titers were negative. Skin biopsies from the back and right abdomen revealed severe lichenoid interface dermatitis (IFD) with numerous dyskeratotic cells mimicking EM and eosinophils; however, direct immunofluorescence of the abdomen biopsy revealed an apparent suprabasal acantholysis with intercellular C3 in the lower half of the epidermis. Histologically, PNP was favored, but indirect immunofluorescence with monkey esophagus IgG was negative.

The skin lesions progressed, and an additional skin biopsy from the left arm performed 1 month later revealed similar histologic features with intercellular IgG and C3 in the lower half of the epidermis with weak basement membrane C3 (Figure 1). Serology also confirmed elevated serum antidesmoglein 1 and 3 antibodies. Thus, in the clinical setting of an erosive mucositis with EM-like and pemphigoidlike eruptions associated with B-cell lymphoma, the patient was diagnosed with PNP.

Although antidesmoglein 3 antibody was shown to be a pathologic driver in PNP, there is a weak correlation between antibody profiles and clinical presentation.⁸ In one case of PNP, antidesmoglein 3 antibody was negative, suggesting that lichenoid IFD may cause the phenotypic findings in PNP.⁹ Thus, the development of nail scarring in PNP may be explained by the presence of lichenoid IFD that is characteristic of PNP. However, the variation in antibody profile in PNP likely is a consequence of epitope spreading.

To the Editor:

Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is an autoimmune mucocutaneous blistering disease that typically occurs secondary to a lymphoproliferative disorder. Paraneoplastic pemphigus is characterized by severe erosive stomatitis, polymorphous skin lesions, and potential bronchiolitis obliterans that can mimic a wide array of conditions. The exact pathogenesis is unknown but is thought to be due to a combination of humoral and cell-mediated immunity. The condition usually confers a poor prognosis, with morbidity from 38% to upwards of 90%.¹

A 47-year-old man developed prominent pink to dusky, ill-defined, targetoid, coalescing papules over the back; violaceous macules over the palms and soles; and numerous crusted oral erosions while hospitalized for an infection. He had a history of stage IVB follicular lymphoma (double-hit type immunoglobulin heavy chain/BCL2 fusion and rearrangement of BCL6) complicated by extensive erosive skin lesions and multiple lines of infections. The clinical differential diagnosis included Stevens-Johnson syndrome vs erythema multiforme (EM) major secondary to administration of oxacillin vs PNP. Herpes simplex virus polymerase chain reaction and Mycoplasma titers were negative. Skin biopsies from the back and right abdomen revealed severe lichenoid interface dermatitis (IFD) with numerous dyskeratotic cells mimicking EM and eosinophils; however, direct immunofluorescence of the abdomen biopsy revealed an apparent suprabasal acantholysis with intercellular C3 in the lower half of the epidermis. Histologically, PNP was favored, but indirect immunofluorescence with monkey esophagus IgG was negative.

The skin lesions progressed, and an additional skin biopsy from the left arm performed 1 month later revealed similar histologic features with intercellular IgG and C3 in the lower half of the epidermis with weak basement membrane C3 (Figure 1). Serology also confirmed elevated serum antidesmoglein 1 and 3 antibodies. Thus, in the clinical setting of an erosive mucositis with EM-like and pemphigoidlike eruptions associated with B-cell lymphoma, the patient was diagnosed with PNP.

Although antidesmoglein 3 antibody was shown to be a pathologic driver in PNP, there is a weak correlation between antibody profiles and clinical presentation.⁸ In one case of PNP, antidesmoglein 3 antibody was negative, suggesting that lichenoid IFD may cause the phenotypic findings in PNP.⁹ Thus, the development of nail scarring in PNP may be explained by the presence of lichenoid IFD that is characteristic of PNP. However, the variation in antibody profile in PNP likely is a consequence of epitope spreading.

To the Editor:

Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multiorgan syndrome, is an autoimmune mucocutaneous blistering disease that typically occurs secondary to a lymphoproliferative disorder. Paraneoplastic pemphigus is characterized by severe erosive stomatitis, polymorphous skin lesions, and potential bronchiolitis obliterans that can mimic a wide array of conditions. The exact pathogenesis is unknown but is thought to be due to a combination of humoral and cell-mediated immunity. The condition usually confers a poor prognosis, with morbidity from 38% to upwards of 90%.¹

A 47-year-old man developed prominent pink to dusky, ill-defined, targetoid, coalescing papules over the back; violaceous macules over the palms and soles; and numerous crusted oral erosions while hospitalized for an infection. He had a history of stage IVB follicular lymphoma (double-hit type immunoglobulin heavy chain/BCL2 fusion and rearrangement of BCL6) complicated by extensive erosive skin lesions and multiple lines of infections. The clinical differential diagnosis included Stevens-Johnson syndrome vs erythema multiforme (EM) major secondary to administration of oxacillin vs PNP. Herpes simplex virus polymerase chain reaction and Mycoplasma titers were negative. Skin biopsies from the back and right abdomen revealed severe lichenoid interface dermatitis (IFD) with numerous dyskeratotic cells mimicking EM and eosinophils; however, direct immunofluorescence of the abdomen biopsy revealed an apparent suprabasal acantholysis with intercellular C3 in the lower half of the epidermis. Histologically, PNP was favored, but indirect immunofluorescence with monkey esophagus IgG was negative.

The skin lesions progressed, and an additional skin biopsy from the left arm performed 1 month later revealed similar histologic features with intercellular IgG and C3 in the lower half of the epidermis with weak basement membrane C3 (Figure 1). Serology also confirmed elevated serum antidesmoglein 1 and 3 antibodies. Thus, in the clinical setting of an erosive mucositis with EM-like and pemphigoidlike eruptions associated with B-cell lymphoma, the patient was diagnosed with PNP.

Although antidesmoglein 3 antibody was shown to be a pathologic driver in PNP, there is a weak correlation between antibody profiles and clinical presentation.⁸ In one case of PNP, antidesmoglein 3 antibody was negative, suggesting that lichenoid IFD may cause the phenotypic findings in PNP.⁹ Thus, the development of nail scarring in PNP may be explained by the presence of lichenoid IFD that is characteristic of PNP. However, the variation in antibody profile in PNP likely is a consequence of epitope spreading.

To the Editor:

Lichen sclerosus is a chronic inflammatory skin disease of unknown cause that predominantly affects the anogenital region, but isolated extragenital lesions occur in 6% to 15% of patients. The buttocks, thighs, neck, shoulder, upper torso, and wrists most commonly are involved; the face rarely is affected.^1,2 Although the etiology of lichen sclerosus remains undetermined, there is growing evidence that autoimmunity may play a role.¹ Lichen sclerosus more commonly is seen in women, and the disease can present at any age, with a bimodal onset in prepubertal children and in postmenopausal women and men in the fourth decade of life.^1-3 A PubMed search of articles indexed for MEDLINE using the terms lichen and eyelid and manually screened revealed 6 cases of lichen sclerosus involving the eyelid.^2-4 We describe a case of lichen sclerosus involving the eyelid and its histopathology.

A 45-year-old woman was referred to dermatology for evaluation of a right lower eyelid lesion of 3 months’ duration. She first noted a small white patch under the eyelid that had doubled in size and felt firm without bleeding or ulceration. Her medical history was unremarkable, and there was no history of ophthalmic conditions, autoimmune disease, trauma, or cancer. An ophthalmic examination was normal, except for a 20×8-mm, flat, depigmented, firm papule with scalloped borders involving the right lower eyelid margin and extending inferiorly without evidence of madarosis or ulceration (Figure 1). She underwent an incisional biopsy that revealed the diagnosis of lichen sclerosus et atrophicus (Figure 2). A full dermatologic evaluation included a genital examination and did not reveal any additional lesions. Tacrolimus ointment was started to avoid the need for long-term use of periocular steroids and their complications.

Histopathology is useful to distinguish among these entities. Although there are no specific features separating lichen sclerosus from a morphea overlap and both entities often are classified by clinical presentation, lichen sclerosus demonstrates epidermal atrophy, follicular plugging, homogenized collagen in the upper dermis with dermal edema, and lichenoid lymphocytic infiltrate (Figure 2).¹ Extragenital lesions in particular also have been noted to have more epidermal atrophy and decreased rete ridges.²

To the Editor:

Lichen sclerosus is a chronic inflammatory skin disease of unknown cause that predominantly affects the anogenital region, but isolated extragenital lesions occur in 6% to 15% of patients. The buttocks, thighs, neck, shoulder, upper torso, and wrists most commonly are involved; the face rarely is affected.^1,2 Although the etiology of lichen sclerosus remains undetermined, there is growing evidence that autoimmunity may play a role.¹ Lichen sclerosus more commonly is seen in women, and the disease can present at any age, with a bimodal onset in prepubertal children and in postmenopausal women and men in the fourth decade of life.^1-3 A PubMed search of articles indexed for MEDLINE using the terms lichen and eyelid and manually screened revealed 6 cases of lichen sclerosus involving the eyelid.^2-4 We describe a case of lichen sclerosus involving the eyelid and its histopathology.

A 45-year-old woman was referred to dermatology for evaluation of a right lower eyelid lesion of 3 months’ duration. She first noted a small white patch under the eyelid that had doubled in size and felt firm without bleeding or ulceration. Her medical history was unremarkable, and there was no history of ophthalmic conditions, autoimmune disease, trauma, or cancer. An ophthalmic examination was normal, except for a 20×8-mm, flat, depigmented, firm papule with scalloped borders involving the right lower eyelid margin and extending inferiorly without evidence of madarosis or ulceration (Figure 1). She underwent an incisional biopsy that revealed the diagnosis of lichen sclerosus et atrophicus (Figure 2). A full dermatologic evaluation included a genital examination and did not reveal any additional lesions. Tacrolimus ointment was started to avoid the need for long-term use of periocular steroids and their complications.

Histopathology is useful to distinguish among these entities. Although there are no specific features separating lichen sclerosus from a morphea overlap and both entities often are classified by clinical presentation, lichen sclerosus demonstrates epidermal atrophy, follicular plugging, homogenized collagen in the upper dermis with dermal edema, and lichenoid lymphocytic infiltrate (Figure 2).¹ Extragenital lesions in particular also have been noted to have more epidermal atrophy and decreased rete ridges.²

To the Editor:

Lichen sclerosus is a chronic inflammatory skin disease of unknown cause that predominantly affects the anogenital region, but isolated extragenital lesions occur in 6% to 15% of patients. The buttocks, thighs, neck, shoulder, upper torso, and wrists most commonly are involved; the face rarely is affected.^1,2 Although the etiology of lichen sclerosus remains undetermined, there is growing evidence that autoimmunity may play a role.¹ Lichen sclerosus more commonly is seen in women, and the disease can present at any age, with a bimodal onset in prepubertal children and in postmenopausal women and men in the fourth decade of life.^1-3 A PubMed search of articles indexed for MEDLINE using the terms lichen and eyelid and manually screened revealed 6 cases of lichen sclerosus involving the eyelid.^2-4 We describe a case of lichen sclerosus involving the eyelid and its histopathology.

A 45-year-old woman was referred to dermatology for evaluation of a right lower eyelid lesion of 3 months’ duration. She first noted a small white patch under the eyelid that had doubled in size and felt firm without bleeding or ulceration. Her medical history was unremarkable, and there was no history of ophthalmic conditions, autoimmune disease, trauma, or cancer. An ophthalmic examination was normal, except for a 20×8-mm, flat, depigmented, firm papule with scalloped borders involving the right lower eyelid margin and extending inferiorly without evidence of madarosis or ulceration (Figure 1). She underwent an incisional biopsy that revealed the diagnosis of lichen sclerosus et atrophicus (Figure 2). A full dermatologic evaluation included a genital examination and did not reveal any additional lesions. Tacrolimus ointment was started to avoid the need for long-term use of periocular steroids and their complications.

Histopathology is useful to distinguish among these entities. Although there are no specific features separating lichen sclerosus from a morphea overlap and both entities often are classified by clinical presentation, lichen sclerosus demonstrates epidermal atrophy, follicular plugging, homogenized collagen in the upper dermis with dermal edema, and lichenoid lymphocytic infiltrate (Figure 2).¹ Extragenital lesions in particular also have been noted to have more epidermal atrophy and decreased rete ridges.²

To the Editor:

Immunosuppressed patients are at particular risk for disseminated mycobacterial infections. A locus minoris resistentiae offers less resistance to the infectious spread of these microorganisms. We present a case of Mycobacterium chelonae infection preferentially involving striae distensae.

A 30-year-old man with chronic eosinophilic pneumonia requiring high-dose corticosteroid therapy presented with widespread skin lesions. He reported no history of cutaneous trauma or aquatic activities. Physical examination revealed the patient was markedly cushingoid with generalized cutaneous atrophy and widespread striae. Multiple erythematous papules surrounded a large ulceration on the dorsal aspect of the left hand. Depressed erythematous plaques and several small crusted erosions extended up the left lower leg (Figure 1) to the knee. Strikingly, numerous brown and pink papules and small plaques on the left thigh were primarily confined within striae (Figure 2).

A biopsy of the left thigh revealed granulomatous inflammation (Figure 3) with numerous acid-fast bacilli (Figure 4). Broad-spectrum coverage for fast-growing acid-fast bacilli with amikacin, ceftriaxone, levofloxacin, and clarithromycin was initiated with steady improvement of the eruption. Tissue culture subsequently grew Mycobacterium abscessus-chelonae, and therapy was narrowed to clarithromycin and moxifloxacin.

Mycobacterium chelonae is a rapidly growing mycobacteria isolated from soil and water worldwide, and human skin is a commensal organism. Cutaneous infections have been associated with traumatic injury, tattooing, surgery, cosmetic procedures, vascular access sites, and acupuncture.¹ Most cases of cutaneous M chelonae infection begin as a violaceous nodule. Over weeks to months, the localized infection progresses to multiple papules, nodules, draining abscesses, or ulcers. Infections tend to disseminate in immunosuppressed patients, and granulomatous inflammation may not be seen.¹

Atypical mycobacterial infection occurring within striae distensae is an example of locus minoris resistentiae—a place of less resistance. Wolf et al² hypothesized that locus minoris resistentiae could explain the occurrence of an isotopic response or the occurrence of a new skin disorder at the site of a previously healed skin condition. They suggested that the same site could be affected by 2 unrelated diseases at different times due to an inherited or acquired susceptibility in the area.² Herpes zoster serves as a primary example of Wolf phenomenon, as numerous conditions including granuloma annulare, pseudolymphoma, Bowen disease, and acne have reportedly emerged in its wake.³

Although locus minoris resistentiae does not specifically involve traumatized skin, it must be distinguished from the Koebner phenomenon, characterized by the appearance of isomorphic lesions in areas of otherwise healthy skin subjected to cutaneous injury, as well as the pseudo-Koebner phenomenon, a similar process involving infectious agents.³

In our patient, striae distensae represented areas of increased predisposition to infection. The catabolic effect of high corticosteroid levels on fibroblast activity decreased collagen deposition in the dermal matrix, leading to the formation of linear bands of atrophic skin.⁴ The elastic fiber network in striae distensae is reduced and reorganized compared to normal skin, in which an intertwining elastic system forms a continuum from the dermoepidermal junction to the deep dermis.⁵ The number of vertically oriented fibrillin microfibrils subjacent to the dermoepidermal junction and elastin fibers in the papillary dermis is comparatively diminished such that the elastin and fibrillin fibers in the deep dermis run more horizontally compared to normal skin.⁴ Consequently, collagen alignment in striae distensae demonstrates more anisotropy, or directionally dependent variability, and the dermal matrix is looser and more floccular than the surrounding skin.⁶ These alterations of dermal architecture likely provide a mechanical advantage for intradermal spread of M chelonae within striae.

Other dermatoses have been observed to occur within striae distensae, specifically leukemia cutis, urticarial vasculitis, lupus erythematosus, keloids, linear focal elastosis, chronic graft-vs-host disease, psoriasis, gestational pemphigoid, and vitiligo.⁷ Given the dissimilarities of these conditions, the distinctive milieu of striae must provide an invitation—a locus minoris resistentiae—for secondary pathology.

Chronic corticosteroid use leads to both immunosuppression and striae distensae, effectively creating a perfect storm for an atypical mycobacterial skin infection demonstrating locus minoris resistentiae. The immunosuppressed state makes patients more susceptible to infection, and striae distensae may serve as a conduit for the offending organisms.

Acknowledgments—We are indebted to Letty Peterson, MD (Vidalia, Georgia), for her referral of this case, and to Stephen Mullins, MD (Augusta, Georgia), for his dermatopathology services.

To the Editor:

Immunosuppressed patients are at particular risk for disseminated mycobacterial infections. A locus minoris resistentiae offers less resistance to the infectious spread of these microorganisms. We present a case of Mycobacterium chelonae infection preferentially involving striae distensae.

A 30-year-old man with chronic eosinophilic pneumonia requiring high-dose corticosteroid therapy presented with widespread skin lesions. He reported no history of cutaneous trauma or aquatic activities. Physical examination revealed the patient was markedly cushingoid with generalized cutaneous atrophy and widespread striae. Multiple erythematous papules surrounded a large ulceration on the dorsal aspect of the left hand. Depressed erythematous plaques and several small crusted erosions extended up the left lower leg (Figure 1) to the knee. Strikingly, numerous brown and pink papules and small plaques on the left thigh were primarily confined within striae (Figure 2).

A biopsy of the left thigh revealed granulomatous inflammation (Figure 3) with numerous acid-fast bacilli (Figure 4). Broad-spectrum coverage for fast-growing acid-fast bacilli with amikacin, ceftriaxone, levofloxacin, and clarithromycin was initiated with steady improvement of the eruption. Tissue culture subsequently grew Mycobacterium abscessus-chelonae, and therapy was narrowed to clarithromycin and moxifloxacin.

Mycobacterium chelonae is a rapidly growing mycobacteria isolated from soil and water worldwide, and human skin is a commensal organism. Cutaneous infections have been associated with traumatic injury, tattooing, surgery, cosmetic procedures, vascular access sites, and acupuncture.¹ Most cases of cutaneous M chelonae infection begin as a violaceous nodule. Over weeks to months, the localized infection progresses to multiple papules, nodules, draining abscesses, or ulcers. Infections tend to disseminate in immunosuppressed patients, and granulomatous inflammation may not be seen.¹

Atypical mycobacterial infection occurring within striae distensae is an example of locus minoris resistentiae—a place of less resistance. Wolf et al² hypothesized that locus minoris resistentiae could explain the occurrence of an isotopic response or the occurrence of a new skin disorder at the site of a previously healed skin condition. They suggested that the same site could be affected by 2 unrelated diseases at different times due to an inherited or acquired susceptibility in the area.² Herpes zoster serves as a primary example of Wolf phenomenon, as numerous conditions including granuloma annulare, pseudolymphoma, Bowen disease, and acne have reportedly emerged in its wake.³

Although locus minoris resistentiae does not specifically involve traumatized skin, it must be distinguished from the Koebner phenomenon, characterized by the appearance of isomorphic lesions in areas of otherwise healthy skin subjected to cutaneous injury, as well as the pseudo-Koebner phenomenon, a similar process involving infectious agents.³

In our patient, striae distensae represented areas of increased predisposition to infection. The catabolic effect of high corticosteroid levels on fibroblast activity decreased collagen deposition in the dermal matrix, leading to the formation of linear bands of atrophic skin.⁴ The elastic fiber network in striae distensae is reduced and reorganized compared to normal skin, in which an intertwining elastic system forms a continuum from the dermoepidermal junction to the deep dermis.⁵ The number of vertically oriented fibrillin microfibrils subjacent to the dermoepidermal junction and elastin fibers in the papillary dermis is comparatively diminished such that the elastin and fibrillin fibers in the deep dermis run more horizontally compared to normal skin.⁴ Consequently, collagen alignment in striae distensae demonstrates more anisotropy, or directionally dependent variability, and the dermal matrix is looser and more floccular than the surrounding skin.⁶ These alterations of dermal architecture likely provide a mechanical advantage for intradermal spread of M chelonae within striae.

Other dermatoses have been observed to occur within striae distensae, specifically leukemia cutis, urticarial vasculitis, lupus erythematosus, keloids, linear focal elastosis, chronic graft-vs-host disease, psoriasis, gestational pemphigoid, and vitiligo.⁷ Given the dissimilarities of these conditions, the distinctive milieu of striae must provide an invitation—a locus minoris resistentiae—for secondary pathology.

Chronic corticosteroid use leads to both immunosuppression and striae distensae, effectively creating a perfect storm for an atypical mycobacterial skin infection demonstrating locus minoris resistentiae. The immunosuppressed state makes patients more susceptible to infection, and striae distensae may serve as a conduit for the offending organisms.

Acknowledgments—We are indebted to Letty Peterson, MD (Vidalia, Georgia), for her referral of this case, and to Stephen Mullins, MD (Augusta, Georgia), for his dermatopathology services.

To the Editor:

Immunosuppressed patients are at particular risk for disseminated mycobacterial infections. A locus minoris resistentiae offers less resistance to the infectious spread of these microorganisms. We present a case of Mycobacterium chelonae infection preferentially involving striae distensae.

A 30-year-old man with chronic eosinophilic pneumonia requiring high-dose corticosteroid therapy presented with widespread skin lesions. He reported no history of cutaneous trauma or aquatic activities. Physical examination revealed the patient was markedly cushingoid with generalized cutaneous atrophy and widespread striae. Multiple erythematous papules surrounded a large ulceration on the dorsal aspect of the left hand. Depressed erythematous plaques and several small crusted erosions extended up the left lower leg (Figure 1) to the knee. Strikingly, numerous brown and pink papules and small plaques on the left thigh were primarily confined within striae (Figure 2).

A biopsy of the left thigh revealed granulomatous inflammation (Figure 3) with numerous acid-fast bacilli (Figure 4). Broad-spectrum coverage for fast-growing acid-fast bacilli with amikacin, ceftriaxone, levofloxacin, and clarithromycin was initiated with steady improvement of the eruption. Tissue culture subsequently grew Mycobacterium abscessus-chelonae, and therapy was narrowed to clarithromycin and moxifloxacin.

Mycobacterium chelonae is a rapidly growing mycobacteria isolated from soil and water worldwide, and human skin is a commensal organism. Cutaneous infections have been associated with traumatic injury, tattooing, surgery, cosmetic procedures, vascular access sites, and acupuncture.¹ Most cases of cutaneous M chelonae infection begin as a violaceous nodule. Over weeks to months, the localized infection progresses to multiple papules, nodules, draining abscesses, or ulcers. Infections tend to disseminate in immunosuppressed patients, and granulomatous inflammation may not be seen.¹

Atypical mycobacterial infection occurring within striae distensae is an example of locus minoris resistentiae—a place of less resistance. Wolf et al² hypothesized that locus minoris resistentiae could explain the occurrence of an isotopic response or the occurrence of a new skin disorder at the site of a previously healed skin condition. They suggested that the same site could be affected by 2 unrelated diseases at different times due to an inherited or acquired susceptibility in the area.² Herpes zoster serves as a primary example of Wolf phenomenon, as numerous conditions including granuloma annulare, pseudolymphoma, Bowen disease, and acne have reportedly emerged in its wake.³

Although locus minoris resistentiae does not specifically involve traumatized skin, it must be distinguished from the Koebner phenomenon, characterized by the appearance of isomorphic lesions in areas of otherwise healthy skin subjected to cutaneous injury, as well as the pseudo-Koebner phenomenon, a similar process involving infectious agents.³

In our patient, striae distensae represented areas of increased predisposition to infection. The catabolic effect of high corticosteroid levels on fibroblast activity decreased collagen deposition in the dermal matrix, leading to the formation of linear bands of atrophic skin.⁴ The elastic fiber network in striae distensae is reduced and reorganized compared to normal skin, in which an intertwining elastic system forms a continuum from the dermoepidermal junction to the deep dermis.⁵ The number of vertically oriented fibrillin microfibrils subjacent to the dermoepidermal junction and elastin fibers in the papillary dermis is comparatively diminished such that the elastin and fibrillin fibers in the deep dermis run more horizontally compared to normal skin.⁴ Consequently, collagen alignment in striae distensae demonstrates more anisotropy, or directionally dependent variability, and the dermal matrix is looser and more floccular than the surrounding skin.⁶ These alterations of dermal architecture likely provide a mechanical advantage for intradermal spread of M chelonae within striae.

Other dermatoses have been observed to occur within striae distensae, specifically leukemia cutis, urticarial vasculitis, lupus erythematosus, keloids, linear focal elastosis, chronic graft-vs-host disease, psoriasis, gestational pemphigoid, and vitiligo.⁷ Given the dissimilarities of these conditions, the distinctive milieu of striae must provide an invitation—a locus minoris resistentiae—for secondary pathology.

Chronic corticosteroid use leads to both immunosuppression and striae distensae, effectively creating a perfect storm for an atypical mycobacterial skin infection demonstrating locus minoris resistentiae. The immunosuppressed state makes patients more susceptible to infection, and striae distensae may serve as a conduit for the offending organisms.

Acknowledgments—We are indebted to Letty Peterson, MD (Vidalia, Georgia), for her referral of this case, and to Stephen Mullins, MD (Augusta, Georgia), for his dermatopathology services.

To the Editor:

Severe dystrophic calcinosis cutis is a debilitating disease with no universally accepted therapeutic options. This case demonstrates the benefit of intravenous (IV) sodium thiosulfate in alleviating the calcified lesions as well as the associated pain and disability. This application of IV sodium thiosulfate with a favorable outcome is new and should be considered for the treatment of generalized dystrophic calcinosis cutis, especially when topical, procedural, or surgical options are not feasible.

A 54-year-old woman with a history of well-controlled dermatomyositis and systemic lupus erythematosus presented with diffuse, hard, calcified lesions on the legs, arms, clavicular region, and neck that had slowly progressed over at least a 10-year period (Figure 1). The lesions were consistent with dystrophic calcinosis cutis. The patient was started on 12.5 g of IV sodium thiosulfate 3 times weekly infused over 30 minutes. Drastic diminution of the cutaneous calcification was observed at 3-month follow-up (Figure 2). She reported decreased pain and burning as well as increased overall functionality and improved sleep. The patient completed 8 months of therapy, but the treatment was stopped secondary to suspicion of a lupuslike flare, and the lesions recurred with more widespread involvement, including the trunk, tendons, bony prominences, and supraclavicular soft tissue. The patient reported burning pain and pruritus that resulted in impairment of daily activities such as getting dressed. Sodium thiosulfate was restarted once weekly, which again resulted in reduction of the dystrophic calcinosis cutis.

Intravenous sodium thiosulfate has been widely used for the treatment of calciphylaxis secondary to end-stage renal failure and tumoral calcinosis.² It also has been reported to be effective in iatrogenic calcinosis cutis secondary to extravasation of calcium-containing solutions in a patient with T-cell acute lymphoblastic leukemia.³ However, reports of its use in treating dystrophic calcinosis cutis are limited. Intravenous sodium thiosulfate—10 g 3 times weekly for 2 weeks, followed by 15 g twice weekly for the next 3 months—was used with abatacept for treatment of dystrophic calcinosis cutis in a patient with juvenile dermatomyositis.⁴ Other formulations of sodium thiosulfate have been reported to result in clearance of calcified lesions, including a topical application compounded in zinc oxide⁵ and intradermal injection at the base of a nodule.⁶ We used 12.5 g over 30 minutes 3 times weekly; however, the dose can be increased to 25 g over 60 minutes if 3 to 4 treatments are tolerated, with nausea being the only notable side effect. Its mechanism of action in treating dystrophic calcinosis cutis is unclear, but it likely is due to its ability to chelate and dissolve calcium deposits. Topical and intradermal therapy is impractical for widespread, dystrophic calcinosis cutis as in our patient.

Our case highlights the successful use of IV sodium thiosulfate as a stand-alone treatment modality for generalized dystrophic calcinosis cutis in an adult patient. Both our patient and a child in a previously reported case who received the same treatment⁴ had dermatomyositis, but we suspect IV sodium thiosulfate also may be effective for dystrophic calcinosis cutis associated with other diseases. Sodium thiosulfate should be considered as a treatment for patients who experience tremendous pain and disability. It is safe, inexpensive, and easy to administer and is especially helpful in patients for whom topical, intradermal, or procedural therapy is not possible.

To the Editor:

Severe dystrophic calcinosis cutis is a debilitating disease with no universally accepted therapeutic options. This case demonstrates the benefit of intravenous (IV) sodium thiosulfate in alleviating the calcified lesions as well as the associated pain and disability. This application of IV sodium thiosulfate with a favorable outcome is new and should be considered for the treatment of generalized dystrophic calcinosis cutis, especially when topical, procedural, or surgical options are not feasible.

A 54-year-old woman with a history of well-controlled dermatomyositis and systemic lupus erythematosus presented with diffuse, hard, calcified lesions on the legs, arms, clavicular region, and neck that had slowly progressed over at least a 10-year period (Figure 1). The lesions were consistent with dystrophic calcinosis cutis. The patient was started on 12.5 g of IV sodium thiosulfate 3 times weekly infused over 30 minutes. Drastic diminution of the cutaneous calcification was observed at 3-month follow-up (Figure 2). She reported decreased pain and burning as well as increased overall functionality and improved sleep. The patient completed 8 months of therapy, but the treatment was stopped secondary to suspicion of a lupuslike flare, and the lesions recurred with more widespread involvement, including the trunk, tendons, bony prominences, and supraclavicular soft tissue. The patient reported burning pain and pruritus that resulted in impairment of daily activities such as getting dressed. Sodium thiosulfate was restarted once weekly, which again resulted in reduction of the dystrophic calcinosis cutis.

Intravenous sodium thiosulfate has been widely used for the treatment of calciphylaxis secondary to end-stage renal failure and tumoral calcinosis.² It also has been reported to be effective in iatrogenic calcinosis cutis secondary to extravasation of calcium-containing solutions in a patient with T-cell acute lymphoblastic leukemia.³ However, reports of its use in treating dystrophic calcinosis cutis are limited. Intravenous sodium thiosulfate—10 g 3 times weekly for 2 weeks, followed by 15 g twice weekly for the next 3 months—was used with abatacept for treatment of dystrophic calcinosis cutis in a patient with juvenile dermatomyositis.⁴ Other formulations of sodium thiosulfate have been reported to result in clearance of calcified lesions, including a topical application compounded in zinc oxide⁵ and intradermal injection at the base of a nodule.⁶ We used 12.5 g over 30 minutes 3 times weekly; however, the dose can be increased to 25 g over 60 minutes if 3 to 4 treatments are tolerated, with nausea being the only notable side effect. Its mechanism of action in treating dystrophic calcinosis cutis is unclear, but it likely is due to its ability to chelate and dissolve calcium deposits. Topical and intradermal therapy is impractical for widespread, dystrophic calcinosis cutis as in our patient.

Our case highlights the successful use of IV sodium thiosulfate as a stand-alone treatment modality for generalized dystrophic calcinosis cutis in an adult patient. Both our patient and a child in a previously reported case who received the same treatment⁴ had dermatomyositis, but we suspect IV sodium thiosulfate also may be effective for dystrophic calcinosis cutis associated with other diseases. Sodium thiosulfate should be considered as a treatment for patients who experience tremendous pain and disability. It is safe, inexpensive, and easy to administer and is especially helpful in patients for whom topical, intradermal, or procedural therapy is not possible.

To the Editor:

Severe dystrophic calcinosis cutis is a debilitating disease with no universally accepted therapeutic options. This case demonstrates the benefit of intravenous (IV) sodium thiosulfate in alleviating the calcified lesions as well as the associated pain and disability. This application of IV sodium thiosulfate with a favorable outcome is new and should be considered for the treatment of generalized dystrophic calcinosis cutis, especially when topical, procedural, or surgical options are not feasible.

A 54-year-old woman with a history of well-controlled dermatomyositis and systemic lupus erythematosus presented with diffuse, hard, calcified lesions on the legs, arms, clavicular region, and neck that had slowly progressed over at least a 10-year period (Figure 1). The lesions were consistent with dystrophic calcinosis cutis. The patient was started on 12.5 g of IV sodium thiosulfate 3 times weekly infused over 30 minutes. Drastic diminution of the cutaneous calcification was observed at 3-month follow-up (Figure 2). She reported decreased pain and burning as well as increased overall functionality and improved sleep. The patient completed 8 months of therapy, but the treatment was stopped secondary to suspicion of a lupuslike flare, and the lesions recurred with more widespread involvement, including the trunk, tendons, bony prominences, and supraclavicular soft tissue. The patient reported burning pain and pruritus that resulted in impairment of daily activities such as getting dressed. Sodium thiosulfate was restarted once weekly, which again resulted in reduction of the dystrophic calcinosis cutis.

Intravenous sodium thiosulfate has been widely used for the treatment of calciphylaxis secondary to end-stage renal failure and tumoral calcinosis.² It also has been reported to be effective in iatrogenic calcinosis cutis secondary to extravasation of calcium-containing solutions in a patient with T-cell acute lymphoblastic leukemia.³ However, reports of its use in treating dystrophic calcinosis cutis are limited. Intravenous sodium thiosulfate—10 g 3 times weekly for 2 weeks, followed by 15 g twice weekly for the next 3 months—was used with abatacept for treatment of dystrophic calcinosis cutis in a patient with juvenile dermatomyositis.⁴ Other formulations of sodium thiosulfate have been reported to result in clearance of calcified lesions, including a topical application compounded in zinc oxide⁵ and intradermal injection at the base of a nodule.⁶ We used 12.5 g over 30 minutes 3 times weekly; however, the dose can be increased to 25 g over 60 minutes if 3 to 4 treatments are tolerated, with nausea being the only notable side effect. Its mechanism of action in treating dystrophic calcinosis cutis is unclear, but it likely is due to its ability to chelate and dissolve calcium deposits. Topical and intradermal therapy is impractical for widespread, dystrophic calcinosis cutis as in our patient.

Our case highlights the successful use of IV sodium thiosulfate as a stand-alone treatment modality for generalized dystrophic calcinosis cutis in an adult patient. Both our patient and a child in a previously reported case who received the same treatment⁴ had dermatomyositis, but we suspect IV sodium thiosulfate also may be effective for dystrophic calcinosis cutis associated with other diseases. Sodium thiosulfate should be considered as a treatment for patients who experience tremendous pain and disability. It is safe, inexpensive, and easy to administer and is especially helpful in patients for whom topical, intradermal, or procedural therapy is not possible.

To the Editor:

The concept of field cancerization has been well described since its initial proposal by Slaughter et al¹ in 1953. It describes a field of genetically altered cells where multiple clonally related neoplasms can develop.^2,3 Treatment of patients with multiple neoplasms within an area of field cancerization can be especially challenging. We report a patient with field cancerization who had multiple squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) that arose within the field.

A 78-year-old man initially presented with a papule on the right forearm of 3 months’ duration. He had a medical history of cutaneous SCC, myocardial infarction, type 2 diabetes mellitus, chronic obstructive pulmonary disease, hypertension, hypercholesterolemia, gout, and diverticulosis. He was not taking any chronic immunosuppressants that may have predisposed him to the development of nonmelanoma skin cancer. The papule was biopsied and diagnosed as a well-differentiated invasive SCC. A month later it was excised with clear margins.

Approximately 5 weeks after the excision, he returned with an enlarging lesion on the right forearm just medial to the excision site. The lesion was biopsied and diagnosed as a well-differentiated SCC. Two months later the lesion was excised with clear margins. Four weeks later he returned with a new lesion adjacent to the medial aspect of the prior excision. The lesion was biopsied and diagnosed as a well-differentiated SCC. Four weeks later the lesion was excised with clear margins.

Another 4 weeks later the patient returned with a new lesion on the excision site. The lesion was biopsied and diagnosed as a well-differentiated SCC. The lesion was treated with radiotherapy, with a 5800-cGy course completed 2 months later. The next month, 2 papules just adjacent to the radiotherapy treatment field were biopsied and diagnosed as well-differentiated SCC, KA type. One week later, 2 additional new papules adjacent to the radiotherapy treatment field were biopsied and diagnosed as moderately differentiated SCC, KA type. At this time, the patient had 4 biopsy-proven KAs on the right forearm in the area of prior radiation (Figure, A). The radiation oncologist felt that further radiation was no longer indicated. A consultation was sought with surgical oncology, and wide excision of the field with sentinel lymph node biopsy and skin grafting was recommended. Computed tomography with contrast of the chest and right arm ordered by surgical oncology did not reveal metastatic disease.

After discussion of the risks, alternatives, and benefits of surgery, the patient elected to try nonsurgical treatment. He was treated with 5-fluorouracil (5-FU) cream 5% twice daily for 4 weeks. It was applied to the right arm from the elbow to the wrist and occluded under an elastic bandage. The patient stated that the biopsy sites became sore and inflamed during the treatment. After 4 weeks of treatment, all 4 KAs had healed without clinical evidence of tumor. During this time, however, the previously treated 2 sites had developed adjacent firm pink papules (Figure, B); these 2 lesions were then treated with intralesional 5-FU 50 mg/mL once weekly to resolution at 4 and 5 weeks, respectively. The proximal lesion was treated with 7.5 mg on week 1 and 5 mg on weeks 2, 3, and 4. The larger distal lesion was treated with 12.5 mg on week 1 and 5 mg on weeks 2, 3, 4, and 5. The volume injected was determined by ability to blanch and indurate the lesion and was decreased due to the shrinking size of the tumor. After 3 injections, both tumors had substantially decreased in size (Figure, C). The patient noted pain during injection but found the procedure tolerable and preferable to surgery. There were no other adverse events. At the end of treatment, both tumors had clinically resolved. No recurrence or development of new tumors was reported over 3 years of follow-up after the last injection.

The development of an expanding neoplastic field appears to play an important role in cutaneous carcinogenesis. It is necessary to consider the cutaneous field cancerization as a highly photodamaged area that contains clinical and subclinical lesions.^2-4 The treatment of cutaneous neoplasms, SCC in particular, should focus not only on the tumor itself but also on the surrounding tissue. Adjunctive field-directed therapies should be considered after treatment of the primary tumor.⁴

Our patient continued to develop SCCs on the right forearm after multiple excisions with clear margins and subsequently was treated with radiation therapy. He then developed 4 KAs after radiation therapy to the right forearm. Topical 5-FU is a well-described treatment of field cancerization.² In our patient, 5-FU cream 5% applied twice daily from the wrist to the elbow under occlusion for 4 weeks led to the involution of all 4 KAs. During this time, our patient developed 2 additional firm pink papules near the previously treated sites, which resolved with intralesional 5-FU weekly for 4 and 5 weeks, respectively.

Intralesional 5-FU has been described for the treatment of multiple and difficult-to-treat KAs. It is an antimetabolite and structural analog of uracil that disrupts DNA and RNA synthesis. It is contraindicated in liver disease, pregnancy or breastfeeding, and allergy to the medication.⁶ Intralesional 5-FU dosing recommendations for KAs include use of a 50-mg/mL solution and injecting 0.1 to 1 mL until the lesion blanches in color, which may be repeated every 1 to 4 weeks.^7,8 The maximum recommended daily dose is 800 mg.⁶ Pretreatment with intralesional 1% lidocaine has been recommended by some authors due to pain with injection.⁸ Recommendations for laboratory monitoring include a complete blood cell count with differential at baseline and weekly. Side effects include local pain, erythema, crusting, ulceration, and necrosis. Systemic side effects include cytopenia and gastrointestinal tract upset.⁶ Intralesional 5-FU has been used successfully in a single dose of 10 mg per lesion in combination with systemic acitretin for the treatment of multiple KAs induced by vemurafenib.⁹ It also has been effective in the treatment of multiple recurrent reactive KAs developing in surgical margins.⁷ A review article reported that the use of intralesional 5-FU produced a 98% cure rate in 56 treated KAs.⁶ Alternative intralesional agents that may be considered for KAs include methotrexate, bleomycin, and interferon alfa-2b.^6,7

Field cancerization may cause the development of multiple clonally related neoplasms within a field of genetically altered cells that may continue to develop after excision with clear margins or radiation therapy. Given the success of treatment in our patient, we recommend consideration for topical and intralesional 5-FU in patients who develop SCCs and KAs within an area of field cancerization.

To the Editor:

The concept of field cancerization has been well described since its initial proposal by Slaughter et al¹ in 1953. It describes a field of genetically altered cells where multiple clonally related neoplasms can develop.^2,3 Treatment of patients with multiple neoplasms within an area of field cancerization can be especially challenging. We report a patient with field cancerization who had multiple squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) that arose within the field.

A 78-year-old man initially presented with a papule on the right forearm of 3 months’ duration. He had a medical history of cutaneous SCC, myocardial infarction, type 2 diabetes mellitus, chronic obstructive pulmonary disease, hypertension, hypercholesterolemia, gout, and diverticulosis. He was not taking any chronic immunosuppressants that may have predisposed him to the development of nonmelanoma skin cancer. The papule was biopsied and diagnosed as a well-differentiated invasive SCC. A month later it was excised with clear margins.

Approximately 5 weeks after the excision, he returned with an enlarging lesion on the right forearm just medial to the excision site. The lesion was biopsied and diagnosed as a well-differentiated SCC. Two months later the lesion was excised with clear margins. Four weeks later he returned with a new lesion adjacent to the medial aspect of the prior excision. The lesion was biopsied and diagnosed as a well-differentiated SCC. Four weeks later the lesion was excised with clear margins.

Another 4 weeks later the patient returned with a new lesion on the excision site. The lesion was biopsied and diagnosed as a well-differentiated SCC. The lesion was treated with radiotherapy, with a 5800-cGy course completed 2 months later. The next month, 2 papules just adjacent to the radiotherapy treatment field were biopsied and diagnosed as well-differentiated SCC, KA type. One week later, 2 additional new papules adjacent to the radiotherapy treatment field were biopsied and diagnosed as moderately differentiated SCC, KA type. At this time, the patient had 4 biopsy-proven KAs on the right forearm in the area of prior radiation (Figure, A). The radiation oncologist felt that further radiation was no longer indicated. A consultation was sought with surgical oncology, and wide excision of the field with sentinel lymph node biopsy and skin grafting was recommended. Computed tomography with contrast of the chest and right arm ordered by surgical oncology did not reveal metastatic disease.

After discussion of the risks, alternatives, and benefits of surgery, the patient elected to try nonsurgical treatment. He was treated with 5-fluorouracil (5-FU) cream 5% twice daily for 4 weeks. It was applied to the right arm from the elbow to the wrist and occluded under an elastic bandage. The patient stated that the biopsy sites became sore and inflamed during the treatment. After 4 weeks of treatment, all 4 KAs had healed without clinical evidence of tumor. During this time, however, the previously treated 2 sites had developed adjacent firm pink papules (Figure, B); these 2 lesions were then treated with intralesional 5-FU 50 mg/mL once weekly to resolution at 4 and 5 weeks, respectively. The proximal lesion was treated with 7.5 mg on week 1 and 5 mg on weeks 2, 3, and 4. The larger distal lesion was treated with 12.5 mg on week 1 and 5 mg on weeks 2, 3, 4, and 5. The volume injected was determined by ability to blanch and indurate the lesion and was decreased due to the shrinking size of the tumor. After 3 injections, both tumors had substantially decreased in size (Figure, C). The patient noted pain during injection but found the procedure tolerable and preferable to surgery. There were no other adverse events. At the end of treatment, both tumors had clinically resolved. No recurrence or development of new tumors was reported over 3 years of follow-up after the last injection.

The development of an expanding neoplastic field appears to play an important role in cutaneous carcinogenesis. It is necessary to consider the cutaneous field cancerization as a highly photodamaged area that contains clinical and subclinical lesions.^2-4 The treatment of cutaneous neoplasms, SCC in particular, should focus not only on the tumor itself but also on the surrounding tissue. Adjunctive field-directed therapies should be considered after treatment of the primary tumor.⁴

Our patient continued to develop SCCs on the right forearm after multiple excisions with clear margins and subsequently was treated with radiation therapy. He then developed 4 KAs after radiation therapy to the right forearm. Topical 5-FU is a well-described treatment of field cancerization.² In our patient, 5-FU cream 5% applied twice daily from the wrist to the elbow under occlusion for 4 weeks led to the involution of all 4 KAs. During this time, our patient developed 2 additional firm pink papules near the previously treated sites, which resolved with intralesional 5-FU weekly for 4 and 5 weeks, respectively.

Intralesional 5-FU has been described for the treatment of multiple and difficult-to-treat KAs. It is an antimetabolite and structural analog of uracil that disrupts DNA and RNA synthesis. It is contraindicated in liver disease, pregnancy or breastfeeding, and allergy to the medication.⁶ Intralesional 5-FU dosing recommendations for KAs include use of a 50-mg/mL solution and injecting 0.1 to 1 mL until the lesion blanches in color, which may be repeated every 1 to 4 weeks.^7,8 The maximum recommended daily dose is 800 mg.⁶ Pretreatment with intralesional 1% lidocaine has been recommended by some authors due to pain with injection.⁸ Recommendations for laboratory monitoring include a complete blood cell count with differential at baseline and weekly. Side effects include local pain, erythema, crusting, ulceration, and necrosis. Systemic side effects include cytopenia and gastrointestinal tract upset.⁶ Intralesional 5-FU has been used successfully in a single dose of 10 mg per lesion in combination with systemic acitretin for the treatment of multiple KAs induced by vemurafenib.⁹ It also has been effective in the treatment of multiple recurrent reactive KAs developing in surgical margins.⁷ A review article reported that the use of intralesional 5-FU produced a 98% cure rate in 56 treated KAs.⁶ Alternative intralesional agents that may be considered for KAs include methotrexate, bleomycin, and interferon alfa-2b.^6,7

Field cancerization may cause the development of multiple clonally related neoplasms within a field of genetically altered cells that may continue to develop after excision with clear margins or radiation therapy. Given the success of treatment in our patient, we recommend consideration for topical and intralesional 5-FU in patients who develop SCCs and KAs within an area of field cancerization.

To the Editor:

The concept of field cancerization has been well described since its initial proposal by Slaughter et al¹ in 1953. It describes a field of genetically altered cells where multiple clonally related neoplasms can develop.^2,3 Treatment of patients with multiple neoplasms within an area of field cancerization can be especially challenging. We report a patient with field cancerization who had multiple squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) that arose within the field.

A 78-year-old man initially presented with a papule on the right forearm of 3 months’ duration. He had a medical history of cutaneous SCC, myocardial infarction, type 2 diabetes mellitus, chronic obstructive pulmonary disease, hypertension, hypercholesterolemia, gout, and diverticulosis. He was not taking any chronic immunosuppressants that may have predisposed him to the development of nonmelanoma skin cancer. The papule was biopsied and diagnosed as a well-differentiated invasive SCC. A month later it was excised with clear margins.

Approximately 5 weeks after the excision, he returned with an enlarging lesion on the right forearm just medial to the excision site. The lesion was biopsied and diagnosed as a well-differentiated SCC. Two months later the lesion was excised with clear margins. Four weeks later he returned with a new lesion adjacent to the medial aspect of the prior excision. The lesion was biopsied and diagnosed as a well-differentiated SCC. Four weeks later the lesion was excised with clear margins.

Another 4 weeks later the patient returned with a new lesion on the excision site. The lesion was biopsied and diagnosed as a well-differentiated SCC. The lesion was treated with radiotherapy, with a 5800-cGy course completed 2 months later. The next month, 2 papules just adjacent to the radiotherapy treatment field were biopsied and diagnosed as well-differentiated SCC, KA type. One week later, 2 additional new papules adjacent to the radiotherapy treatment field were biopsied and diagnosed as moderately differentiated SCC, KA type. At this time, the patient had 4 biopsy-proven KAs on the right forearm in the area of prior radiation (Figure, A). The radiation oncologist felt that further radiation was no longer indicated. A consultation was sought with surgical oncology, and wide excision of the field with sentinel lymph node biopsy and skin grafting was recommended. Computed tomography with contrast of the chest and right arm ordered by surgical oncology did not reveal metastatic disease.

After discussion of the risks, alternatives, and benefits of surgery, the patient elected to try nonsurgical treatment. He was treated with 5-fluorouracil (5-FU) cream 5% twice daily for 4 weeks. It was applied to the right arm from the elbow to the wrist and occluded under an elastic bandage. The patient stated that the biopsy sites became sore and inflamed during the treatment. After 4 weeks of treatment, all 4 KAs had healed without clinical evidence of tumor. During this time, however, the previously treated 2 sites had developed adjacent firm pink papules (Figure, B); these 2 lesions were then treated with intralesional 5-FU 50 mg/mL once weekly to resolution at 4 and 5 weeks, respectively. The proximal lesion was treated with 7.5 mg on week 1 and 5 mg on weeks 2, 3, and 4. The larger distal lesion was treated with 12.5 mg on week 1 and 5 mg on weeks 2, 3, 4, and 5. The volume injected was determined by ability to blanch and indurate the lesion and was decreased due to the shrinking size of the tumor. After 3 injections, both tumors had substantially decreased in size (Figure, C). The patient noted pain during injection but found the procedure tolerable and preferable to surgery. There were no other adverse events. At the end of treatment, both tumors had clinically resolved. No recurrence or development of new tumors was reported over 3 years of follow-up after the last injection.

The development of an expanding neoplastic field appears to play an important role in cutaneous carcinogenesis. It is necessary to consider the cutaneous field cancerization as a highly photodamaged area that contains clinical and subclinical lesions.^2-4 The treatment of cutaneous neoplasms, SCC in particular, should focus not only on the tumor itself but also on the surrounding tissue. Adjunctive field-directed therapies should be considered after treatment of the primary tumor.⁴

Our patient continued to develop SCCs on the right forearm after multiple excisions with clear margins and subsequently was treated with radiation therapy. He then developed 4 KAs after radiation therapy to the right forearm. Topical 5-FU is a well-described treatment of field cancerization.² In our patient, 5-FU cream 5% applied twice daily from the wrist to the elbow under occlusion for 4 weeks led to the involution of all 4 KAs. During this time, our patient developed 2 additional firm pink papules near the previously treated sites, which resolved with intralesional 5-FU weekly for 4 and 5 weeks, respectively.

Intralesional 5-FU has been described for the treatment of multiple and difficult-to-treat KAs. It is an antimetabolite and structural analog of uracil that disrupts DNA and RNA synthesis. It is contraindicated in liver disease, pregnancy or breastfeeding, and allergy to the medication.⁶ Intralesional 5-FU dosing recommendations for KAs include use of a 50-mg/mL solution and injecting 0.1 to 1 mL until the lesion blanches in color, which may be repeated every 1 to 4 weeks.^7,8 The maximum recommended daily dose is 800 mg.⁶ Pretreatment with intralesional 1% lidocaine has been recommended by some authors due to pain with injection.⁸ Recommendations for laboratory monitoring include a complete blood cell count with differential at baseline and weekly. Side effects include local pain, erythema, crusting, ulceration, and necrosis. Systemic side effects include cytopenia and gastrointestinal tract upset.⁶ Intralesional 5-FU has been used successfully in a single dose of 10 mg per lesion in combination with systemic acitretin for the treatment of multiple KAs induced by vemurafenib.⁹ It also has been effective in the treatment of multiple recurrent reactive KAs developing in surgical margins.⁷ A review article reported that the use of intralesional 5-FU produced a 98% cure rate in 56 treated KAs.⁶ Alternative intralesional agents that may be considered for KAs include methotrexate, bleomycin, and interferon alfa-2b.^6,7

Field cancerization may cause the development of multiple clonally related neoplasms within a field of genetically altered cells that may continue to develop after excision with clear margins or radiation therapy. Given the success of treatment in our patient, we recommend consideration for topical and intralesional 5-FU in patients who develop SCCs and KAs within an area of field cancerization.

To the Editor: 

Palmoplantar lichen planus (LP) is an uncommon variant of LP that involves the palms and soles. The prevalence of LP is approximately 0.1% to 2% in the general population. It can affect both mucosal and cutaneous surfaces.¹ A study of 36 patients with LP showed that 25% (9/36) had palmar and/or plantar involvement.² Palmoplantar LP is more commonly found in men than women, with an average age of onset of 38 to 65 years.³ It tends to affect the soles more often than the palms, with the most common site being the plantar arch. Itching generally is the most common symptom reported. Lesions often resolve over a few months, but relapses can occur in 10% to 29% of patients.² The clinical morphology commonly is characterized as erythematous scaly plaques, hyperkeratotic plaques, or ulcerations.⁴ Due to its rare occurrence, palmoplantar LP often is misdiagnosed as psoriasis, eczematous dermatitis, tinea nigra, or secondary syphilis, making pathology extremely helpful in making the diagnosis.¹ Darker skin types can obscure defining characteristics, further impeding a timely diagnosis. We describe a novel case of palmoplantar LP that was successfully treated with methotrexate.  

A 38-year-old man with no notable medical history presented for dermatologic evaluation of a palmar and plantar rash of 4 months' duration. The rash was accompanied by intense burning pain and pruritus. Prior to presentation, he had been treated with multiple prednisone tapers starting at 40 mg daily as well as combination therapy of a 2-week course of minocycline 100 mg twice daily and clobetasol ointment twice daily for 4 months, with no notable improvement. Workup prior to presentation included a negative potassium hydroxide fungal preparation and a normal antinuclear antibody titer. A review of symptoms was negative for arthralgia, myalgia, photosensitivity, malar rash, Raynaud phenomenon, pleuritic pain, seizures, and psychosis.  

Physical examination revealed focal areas of mildly thick, hyperkeratotic scale with desquamation on the plantar and palmar surfaces of the feet and hands. The underlying skin of the feet consisted of dyspigmented patches of dark brown and hypopigmented skin with erythema, profound scaling, and sparing of the internal plantar arches (Figure 1A). On the palms, thin hyperkeratotic plaques with desquamation and erythematous maceration of the surrounding skin were observed (Figure 2A). Thin white plaques of the posterior bilateral buccal mucosa were appreciated as well as an erosion that extended to the lower lip.  

The differential diagnosis included LP, psoriasis, acquired palmoplantar keratoderma, and discoid lupus erythematosus. Tinea pedis and tinea manuum were less likely in the setting of a negative potassium hydroxide fungal preparation.  

A biopsy of the lateral aspect of the left foot showed a cell-poor interface dermatitis that could resemble partially treated LP or a lichenoid hypersensitivity reaction (Figure 3). Given the clinical and pathologic findings, a diagnosis of palmoplantar LP was favored. The patient was on no medications or over-the-counter supplements prior to the appearance of the rash, making a lichenoid hypersensitivity rash less likely. The histology findings likely were muted, as they were done at the end of the prednisone taper. 

Minocycline and clobetasol ointment were discontinued, and the prednisone taper was completed as originally prescribed. The patient was started on 25 mg daily of acitretin for 4 weeks, then increased to 35 mg daily. Notable improvement in the palmar and plantar lesions was noted after the initial 4 weeks of therapy; however, acitretin treatment was discontinued due to lack of adequate insurance coverage for the medication. The patient became symptomatic several weeks following acitretin cessation and was started on methotrexate 15 mg weekly with triamcinolone acetonide paste 0.1% for the oral lesions. Once again, improvement was seen on both the palmar and plantar surfaces after 4 weeks of therapy (Figures 1B and 2B). 

Evidence for treatment of palmoplantar LP is limited to a few case reports and case series. Documented treatments for palmoplantar LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive medications.⁴ One case report described a patient who responded well to prednisone therapy (1 mg/kg daily for 3 weeks, then reduced to 5 mg daily).⁵ Another report described a patient who responded favorably to cyclosporine 3.5 mg/kg daily for 4 weeks, then tapered over another 4 weeks for a total of 8 weeks of treatment.⁴ Although the most common treatments described in the literature consist of acitretin as well as topical and systemic steroids, few have discussed the efficacy of methotrexate. In one study, acitretin did not result in clearance, but the patient saw profound improvement with methotrexate (titrated up to 25 mg weekly) over 2 months.¹  

In our case, treatment with methotrexate was proven successful in a patient who responded to acitretin but was unable to afford treatment. This case highlights a rare variant of a common disease and the possibility of methotrexate as a cost-effective and useful treatment option for LP.  

To the Editor: 

Palmoplantar lichen planus (LP) is an uncommon variant of LP that involves the palms and soles. The prevalence of LP is approximately 0.1% to 2% in the general population. It can affect both mucosal and cutaneous surfaces.¹ A study of 36 patients with LP showed that 25% (9/36) had palmar and/or plantar involvement.² Palmoplantar LP is more commonly found in men than women, with an average age of onset of 38 to 65 years.³ It tends to affect the soles more often than the palms, with the most common site being the plantar arch. Itching generally is the most common symptom reported. Lesions often resolve over a few months, but relapses can occur in 10% to 29% of patients.² The clinical morphology commonly is characterized as erythematous scaly plaques, hyperkeratotic plaques, or ulcerations.⁴ Due to its rare occurrence, palmoplantar LP often is misdiagnosed as psoriasis, eczematous dermatitis, tinea nigra, or secondary syphilis, making pathology extremely helpful in making the diagnosis.¹ Darker skin types can obscure defining characteristics, further impeding a timely diagnosis. We describe a novel case of palmoplantar LP that was successfully treated with methotrexate.  

A 38-year-old man with no notable medical history presented for dermatologic evaluation of a palmar and plantar rash of 4 months' duration. The rash was accompanied by intense burning pain and pruritus. Prior to presentation, he had been treated with multiple prednisone tapers starting at 40 mg daily as well as combination therapy of a 2-week course of minocycline 100 mg twice daily and clobetasol ointment twice daily for 4 months, with no notable improvement. Workup prior to presentation included a negative potassium hydroxide fungal preparation and a normal antinuclear antibody titer. A review of symptoms was negative for arthralgia, myalgia, photosensitivity, malar rash, Raynaud phenomenon, pleuritic pain, seizures, and psychosis.  

Physical examination revealed focal areas of mildly thick, hyperkeratotic scale with desquamation on the plantar and palmar surfaces of the feet and hands. The underlying skin of the feet consisted of dyspigmented patches of dark brown and hypopigmented skin with erythema, profound scaling, and sparing of the internal plantar arches (Figure 1A). On the palms, thin hyperkeratotic plaques with desquamation and erythematous maceration of the surrounding skin were observed (Figure 2A). Thin white plaques of the posterior bilateral buccal mucosa were appreciated as well as an erosion that extended to the lower lip.  

The differential diagnosis included LP, psoriasis, acquired palmoplantar keratoderma, and discoid lupus erythematosus. Tinea pedis and tinea manuum were less likely in the setting of a negative potassium hydroxide fungal preparation.  

A biopsy of the lateral aspect of the left foot showed a cell-poor interface dermatitis that could resemble partially treated LP or a lichenoid hypersensitivity reaction (Figure 3). Given the clinical and pathologic findings, a diagnosis of palmoplantar LP was favored. The patient was on no medications or over-the-counter supplements prior to the appearance of the rash, making a lichenoid hypersensitivity rash less likely. The histology findings likely were muted, as they were done at the end of the prednisone taper. 

Minocycline and clobetasol ointment were discontinued, and the prednisone taper was completed as originally prescribed. The patient was started on 25 mg daily of acitretin for 4 weeks, then increased to 35 mg daily. Notable improvement in the palmar and plantar lesions was noted after the initial 4 weeks of therapy; however, acitretin treatment was discontinued due to lack of adequate insurance coverage for the medication. The patient became symptomatic several weeks following acitretin cessation and was started on methotrexate 15 mg weekly with triamcinolone acetonide paste 0.1% for the oral lesions. Once again, improvement was seen on both the palmar and plantar surfaces after 4 weeks of therapy (Figures 1B and 2B). 

Evidence for treatment of palmoplantar LP is limited to a few case reports and case series. Documented treatments for palmoplantar LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive medications.⁴ One case report described a patient who responded well to prednisone therapy (1 mg/kg daily for 3 weeks, then reduced to 5 mg daily).⁵ Another report described a patient who responded favorably to cyclosporine 3.5 mg/kg daily for 4 weeks, then tapered over another 4 weeks for a total of 8 weeks of treatment.⁴ Although the most common treatments described in the literature consist of acitretin as well as topical and systemic steroids, few have discussed the efficacy of methotrexate. In one study, acitretin did not result in clearance, but the patient saw profound improvement with methotrexate (titrated up to 25 mg weekly) over 2 months.¹  

In our case, treatment with methotrexate was proven successful in a patient who responded to acitretin but was unable to afford treatment. This case highlights a rare variant of a common disease and the possibility of methotrexate as a cost-effective and useful treatment option for LP.  

To the Editor: 

Palmoplantar lichen planus (LP) is an uncommon variant of LP that involves the palms and soles. The prevalence of LP is approximately 0.1% to 2% in the general population. It can affect both mucosal and cutaneous surfaces.¹ A study of 36 patients with LP showed that 25% (9/36) had palmar and/or plantar involvement.² Palmoplantar LP is more commonly found in men than women, with an average age of onset of 38 to 65 years.³ It tends to affect the soles more often than the palms, with the most common site being the plantar arch. Itching generally is the most common symptom reported. Lesions often resolve over a few months, but relapses can occur in 10% to 29% of patients.² The clinical morphology commonly is characterized as erythematous scaly plaques, hyperkeratotic plaques, or ulcerations.⁴ Due to its rare occurrence, palmoplantar LP often is misdiagnosed as psoriasis, eczematous dermatitis, tinea nigra, or secondary syphilis, making pathology extremely helpful in making the diagnosis.¹ Darker skin types can obscure defining characteristics, further impeding a timely diagnosis. We describe a novel case of palmoplantar LP that was successfully treated with methotrexate.  

A 38-year-old man with no notable medical history presented for dermatologic evaluation of a palmar and plantar rash of 4 months' duration. The rash was accompanied by intense burning pain and pruritus. Prior to presentation, he had been treated with multiple prednisone tapers starting at 40 mg daily as well as combination therapy of a 2-week course of minocycline 100 mg twice daily and clobetasol ointment twice daily for 4 months, with no notable improvement. Workup prior to presentation included a negative potassium hydroxide fungal preparation and a normal antinuclear antibody titer. A review of symptoms was negative for arthralgia, myalgia, photosensitivity, malar rash, Raynaud phenomenon, pleuritic pain, seizures, and psychosis.  

Physical examination revealed focal areas of mildly thick, hyperkeratotic scale with desquamation on the plantar and palmar surfaces of the feet and hands. The underlying skin of the feet consisted of dyspigmented patches of dark brown and hypopigmented skin with erythema, profound scaling, and sparing of the internal plantar arches (Figure 1A). On the palms, thin hyperkeratotic plaques with desquamation and erythematous maceration of the surrounding skin were observed (Figure 2A). Thin white plaques of the posterior bilateral buccal mucosa were appreciated as well as an erosion that extended to the lower lip.  

The differential diagnosis included LP, psoriasis, acquired palmoplantar keratoderma, and discoid lupus erythematosus. Tinea pedis and tinea manuum were less likely in the setting of a negative potassium hydroxide fungal preparation.  

A biopsy of the lateral aspect of the left foot showed a cell-poor interface dermatitis that could resemble partially treated LP or a lichenoid hypersensitivity reaction (Figure 3). Given the clinical and pathologic findings, a diagnosis of palmoplantar LP was favored. The patient was on no medications or over-the-counter supplements prior to the appearance of the rash, making a lichenoid hypersensitivity rash less likely. The histology findings likely were muted, as they were done at the end of the prednisone taper. 

Minocycline and clobetasol ointment were discontinued, and the prednisone taper was completed as originally prescribed. The patient was started on 25 mg daily of acitretin for 4 weeks, then increased to 35 mg daily. Notable improvement in the palmar and plantar lesions was noted after the initial 4 weeks of therapy; however, acitretin treatment was discontinued due to lack of adequate insurance coverage for the medication. The patient became symptomatic several weeks following acitretin cessation and was started on methotrexate 15 mg weekly with triamcinolone acetonide paste 0.1% for the oral lesions. Once again, improvement was seen on both the palmar and plantar surfaces after 4 weeks of therapy (Figures 1B and 2B). 

Evidence for treatment of palmoplantar LP is limited to a few case reports and case series. Documented treatments for palmoplantar LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive medications.⁴ One case report described a patient who responded well to prednisone therapy (1 mg/kg daily for 3 weeks, then reduced to 5 mg daily).⁵ Another report described a patient who responded favorably to cyclosporine 3.5 mg/kg daily for 4 weeks, then tapered over another 4 weeks for a total of 8 weeks of treatment.⁴ Although the most common treatments described in the literature consist of acitretin as well as topical and systemic steroids, few have discussed the efficacy of methotrexate. In one study, acitretin did not result in clearance, but the patient saw profound improvement with methotrexate (titrated up to 25 mg weekly) over 2 months.¹  

In our case, treatment with methotrexate was proven successful in a patient who responded to acitretin but was unable to afford treatment. This case highlights a rare variant of a common disease and the possibility of methotrexate as a cost-effective and useful treatment option for LP.