CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Diclofenac-induced pseudoporphyria; an under-recognized condition? N. Turnbull,1 M. Callan2 and R. C. D. Staughton3 1 Pathology Department, Warwick Hospital, Warwick, UK; Departments of 2Rheumatology and 3Dermatology, Chelsea and Westminster Hospital, London, UK
doi:10.1111/ced.12313
Summary
Pseudoporphyria is a photodistributed bullous disorder that is clinically and histologically similar to porphyria cutanea tarda (PCT), but without abnormal porphyrin biochemistry. Renal failure, dialysis, excessive ultraviolet A and medications, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), have been associated with pseudoporphyria. We report a case of diclofenac-induced pseudoporphyria in a man with psoriatic arthritis. To our knowledge, this is only the second reported case of pseudoporphyria associated with diclofenac. Diclofenac has hitherto been considered by many dermatologists as a safe alternative in NSAID-induced pseudoporphyria.
Pseudoporphyria is a well recognized but uncommon condition. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading cause of drug-induced pseudoporphyria, naproxen being the most commonly reported. Diclofenac has hitherto been considered a safe alternative in patients with NSAID-related pseudoporphyria for whom ongoing treatment is required. We describe a case of diclofenac-induced pseudoporphyria in a man with psoriatic arthritis. We believe this to be only the second report of pseudoporphryia related to the use of diclofenac.
Report A 40-year-old male solicitor was seen in our clinic with skin fragility of the dorsa of his hands. He was an American who had returned to Texas for a summer holiday. On his return to the UK, he noticed that when he knocked the dorsa of his hands, the skin would tear easily. He had sought advice 3 months earCorrespondence: Dr Nick Turnbull, Pathology Department, Warwick Hospital, Warwick, Warwickshire, CV34 5BW, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 13 December 2013
348
Clinical and Experimental Dermatology (2014) 39, pp348–350
lier with a right knee effusion and mild synovitis affecting the distal interphalangeal joint of the left little finger and the interphalangeal joints of the left great toe. He had a history of cutaneous and nail psoriasis, and a diagnosis of psoriatic arthritis was made at that time. The knee effusion was aspirated and the joint injected with depomedrone. He was prescribed diclofenac 50 mg three times daily. This was the only medication that he was taking regularly at the time of his presentation with skin fragility. He did not smoke or drink. There was no family or personal history of any medical illnesses. He was not known to have any drug allergies. He reported that the skin fragility had been worse while he was in Texas, where he had significantly more sun exposure. On physical examination, the patient was seen to have thin and scarred skin on the dorsum of both hands, with these features being more noticeable on the right than the left hand (Fig. 1). There were no vesicles, bullae, milia or hypertrichosis. The rest of his skin was unremarkable. A clinical diagnosis of pseudoporphyria was considered, and photoprotection strategies were advised. A biopsy was taken, but the histological findings were non contributory. Blood, fecal and urinary porphyria screens were negative. Diclofenac was discontinued, and the patient was started on methotrex-
ª 2014 British Association of Dermatologists
Diclofenac induced pseudoporphyria: an under-recognized condition? N. Turnbull et al.
Figure 1 Dorsum of right hand, showing atrophic skin and
purpura.
ate by his rheumatologist. A 3-month period without skin fragility followed, after which the methotrexate had to be stopped owing to the development of abnormal liver function test results. For a short period, the patient managed his arthritis with paracetamol and codeine, but was soon so troubled with his symptoms that he was restarted on diclofenac, which led to recurrence of the skin fragility within a few weeks. He has now been started on sulfasalazine, has stopped taking diclofenac, and the fragility has settled again. Pseudoporphyria is a well recognized but uncommon phenomenon, which has been associated with renal failure, dialysis, excessive sun exposure, tanning beds, light therapy, various medications and even cola drinks. It is characterized by erythema, skin fragility, blister formation and photosensitivity. These signs occur on sun-exposed skin, particularly the hands and feet. Often, fragility and bruising may be the only clinical signs. The clinical and histological features of pseudoporphyria can be subtle or indistinguishable from porphyria cutanea tarda; however, pseudoporphyria does not usually demonstrate hypertrichosis or scleroderma-like skin changes, and is not associated with altered plasma or urinary porphyrin level.1 Medications, particularly NSAIDs, are frequently implicated in pseudoporphyria. The condition may be under-recognized. Lang and Finlayson found that 12% of children with juvenile idiopathic arthritis on longterm NSAID treatment developed pseudoporphyria.2 Many of these children were taking naproxen, which is the most common drug implicated in the development of pseudoporphyria.3
ª 2014 British Association of Dermatologists
The mechanism by which NSAIDs cause clinical pseudoporphyria is still unclear, although a phototoxic mechanism has been suggested, with production of singlet oxygen after ultraviolet (UV)A radiation exposure. Light in the UVA range is proposed to be critical in the pathogenesis of pseudoporphyria, although its exact role is not yet elucidated.1 NSAIDs are one of the most common drugs associated with adverse skin reactions. The incidence of such reactions is difficult to estimate as NSAIDs can be purchased without prescription, and patients may not seek medical assistance for all reactions. In a prospective study of 20 000 patients, the incidence of NSAIDassociated cutaneous adverse effects was reported as 0.3%.4 NSAID-associated cutaneous adverse reactions include morbilliform drug exanthema, urticaria, serum sickness-like reaction, lichenoid eruptions, acute generalized exanthematous pustulosis, pemphigoid reactions and photosensitivity.5 NSAIDs may exacerbate preexisting conditions such as psoriasis, and may rarely cause serious adverse skin events such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug rash with eosinophilia and systemic symptoms (DRESS).6,7 Topical NSAIDs have been associated with allergic contact dermatitis and with phototoxic and photoallergic contact dermatitis, although the incidence of serious photoallergic reaction while using these agents is extremely rare.8 Of the NSAIDs, those of the propionic acid derivative group, such as naproxen, are the most recognized to cause pseudoporphyria, and the reaction appears unrelated to dose.3 The newer cyclo-oxygenase (COX) 2 inhibitors are not without risk, as celecoxib has now been associated with pseudoporphyria as well.9 Diclofenac is an acetic acid derivative, and had been suggested as a safe alternative NSAID in patients with NSAID-related pseudoporphyria for whom ongoing treatment is required. However, in 2001, diclofenac was reported to have caused pseudoporphyria in a 57-year-old Spanish woman with seronegative rheumatoid arthritis;10 she had been taking diclofenac for 3 months before onset of the pseudoporphyria, and the condition ceased after this medication was stopped. To our knowledge, our patient is only the second reported case of diclofenac-associated pseudoporphyria. Pseudoporphyria induced by diclofenac is vanishingly rare; however, awareness of this scarce association is important for patients requiring ongoing management with NSAIDs.
Clinical and Experimental Dermatology (2014) 39, pp348–350
349
Diclofenac induced pseudoporphyria: an under-recognized condition? N. Turnbull et al.
Learning points ● Pseudoporphyria is a photodistributed bullous
disorder, which is clinically and histologically similar to PCT, but without abnormal porphyrin biochemistry testing. ● Renal failure, dialysis, excessive UVA and medications (particularly the NSAIDs) have been associated with pseudoporphyria. ● To our knowledge, this is only the second reported case in the literature of pseudoporphyria associated with diclofenac, which is considered by many dermatologists as a safe alternative agent in NSAID-induced pseudoporphyria.
References 1 Green JJ, Manders SM. Pseudoporphyria. J Am Acad Dermatol 2001; 44: 100–8. 2 Lang BA, Finlayson LA. Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis. J Pediatr 1994; 124: 639–42.
350
Clinical and Experimental Dermatology (2014) 39, pp348–350
3 O’Donoghue NB, Higgins EM. Case 1: Naproxen-induced pseudoporphyria. Clin Exp Dermatol 2002; 27: 339–40. 4 Kaiser U, Sollberger J, Hoigne R et al. Skin side effects of nonsteroidal anti-inflammatory analgesics and so called minor analgesics. Wochenschr 1987; 117: 1966–70. 5 Sanchez-Borges M, Capriles-Hullett A, Caballero-Fonseca F. Risk of skin reactions when using ibuprofen-based medicines. Expert Opin Drug Saf 2005; 4: 837–48. 6 Ungprasert P, Kittanamongkolchai W, Price C et al. What is the ‘safest” non-steroidal anti-inflammatory drugs? Am Med J 2012; 3: 115–23. 7 Lee JH, Park HK, Heo J et al. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome induced by celecoxib and antituberculosis drugs. J Korean Med Sci 2008; 23: 521–5. 8 Jenerowicz D, Jakubowicz O, Polanska A et al. Photosensitivity to selected topical nonsteroidal anti-inflammatory drugs preparations – a review of literature data and author’s own experience. Cent Eur J Immunol 2011; 36: 197–203. 9 Cummins R, Wagner-Weiner L, Paller A. Pseudoporphyria induced by celecoxib in a patient with juvenile rheumatoid arthritis. J Rheumatol 2000; 27: 2938–40. 10 Zaballos P, Ara M, Echevarra V et al. Pseudoporphyria induced by diclofenac. Atcas Dermosifiliogr 2001; 92: 578–81.
ª 2014 British Association of Dermatologists
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Diclofenac-induced pseudoporphyria; an under-recognized condition? N. Turnbull,1 M. Callan2 and R. C. D. Staughton3 1 Pathology Department, Warwick Hospital, Warwick, UK; Departments of 2Rheumatology and 3Dermatology, Chelsea and Westminster Hospital, London, UK
doi:10.1111/ced.12313
Summary
Pseudoporphyria is a photodistributed bullous disorder that is clinically and histologically similar to porphyria cutanea tarda (PCT), but without abnormal porphyrin biochemistry. Renal failure, dialysis, excessive ultraviolet A and medications, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), have been associated with pseudoporphyria. We report a case of diclofenac-induced pseudoporphyria in a man with psoriatic arthritis. To our knowledge, this is only the second reported case of pseudoporphyria associated with diclofenac. Diclofenac has hitherto been considered by many dermatologists as a safe alternative in NSAID-induced pseudoporphyria.
Pseudoporphyria is a well recognized but uncommon condition. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading cause of drug-induced pseudoporphyria, naproxen being the most commonly reported. Diclofenac has hitherto been considered a safe alternative in patients with NSAID-related pseudoporphyria for whom ongoing treatment is required. We describe a case of diclofenac-induced pseudoporphyria in a man with psoriatic arthritis. We believe this to be only the second report of pseudoporphryia related to the use of diclofenac.
Report A 40-year-old male solicitor was seen in our clinic with skin fragility of the dorsa of his hands. He was an American who had returned to Texas for a summer holiday. On his return to the UK, he noticed that when he knocked the dorsa of his hands, the skin would tear easily. He had sought advice 3 months earCorrespondence: Dr Nick Turnbull, Pathology Department, Warwick Hospital, Warwick, Warwickshire, CV34 5BW, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 13 December 2013
348
Clinical and Experimental Dermatology (2014) 39, pp348–350
lier with a right knee effusion and mild synovitis affecting the distal interphalangeal joint of the left little finger and the interphalangeal joints of the left great toe. He had a history of cutaneous and nail psoriasis, and a diagnosis of psoriatic arthritis was made at that time. The knee effusion was aspirated and the joint injected with depomedrone. He was prescribed diclofenac 50 mg three times daily. This was the only medication that he was taking regularly at the time of his presentation with skin fragility. He did not smoke or drink. There was no family or personal history of any medical illnesses. He was not known to have any drug allergies. He reported that the skin fragility had been worse while he was in Texas, where he had significantly more sun exposure. On physical examination, the patient was seen to have thin and scarred skin on the dorsum of both hands, with these features being more noticeable on the right than the left hand (Fig. 1). There were no vesicles, bullae, milia or hypertrichosis. The rest of his skin was unremarkable. A clinical diagnosis of pseudoporphyria was considered, and photoprotection strategies were advised. A biopsy was taken, but the histological findings were non contributory. Blood, fecal and urinary porphyria screens were negative. Diclofenac was discontinued, and the patient was started on methotrex-
ª 2014 British Association of Dermatologists
Diclofenac induced pseudoporphyria: an under-recognized condition? N. Turnbull et al.
Figure 1 Dorsum of right hand, showing atrophic skin and
purpura.
ate by his rheumatologist. A 3-month period without skin fragility followed, after which the methotrexate had to be stopped owing to the development of abnormal liver function test results. For a short period, the patient managed his arthritis with paracetamol and codeine, but was soon so troubled with his symptoms that he was restarted on diclofenac, which led to recurrence of the skin fragility within a few weeks. He has now been started on sulfasalazine, has stopped taking diclofenac, and the fragility has settled again. Pseudoporphyria is a well recognized but uncommon phenomenon, which has been associated with renal failure, dialysis, excessive sun exposure, tanning beds, light therapy, various medications and even cola drinks. It is characterized by erythema, skin fragility, blister formation and photosensitivity. These signs occur on sun-exposed skin, particularly the hands and feet. Often, fragility and bruising may be the only clinical signs. The clinical and histological features of pseudoporphyria can be subtle or indistinguishable from porphyria cutanea tarda; however, pseudoporphyria does not usually demonstrate hypertrichosis or scleroderma-like skin changes, and is not associated with altered plasma or urinary porphyrin level.1 Medications, particularly NSAIDs, are frequently implicated in pseudoporphyria. The condition may be under-recognized. Lang and Finlayson found that 12% of children with juvenile idiopathic arthritis on longterm NSAID treatment developed pseudoporphyria.2 Many of these children were taking naproxen, which is the most common drug implicated in the development of pseudoporphyria.3
ª 2014 British Association of Dermatologists
The mechanism by which NSAIDs cause clinical pseudoporphyria is still unclear, although a phototoxic mechanism has been suggested, with production of singlet oxygen after ultraviolet (UV)A radiation exposure. Light in the UVA range is proposed to be critical in the pathogenesis of pseudoporphyria, although its exact role is not yet elucidated.1 NSAIDs are one of the most common drugs associated with adverse skin reactions. The incidence of such reactions is difficult to estimate as NSAIDs can be purchased without prescription, and patients may not seek medical assistance for all reactions. In a prospective study of 20 000 patients, the incidence of NSAIDassociated cutaneous adverse effects was reported as 0.3%.4 NSAID-associated cutaneous adverse reactions include morbilliform drug exanthema, urticaria, serum sickness-like reaction, lichenoid eruptions, acute generalized exanthematous pustulosis, pemphigoid reactions and photosensitivity.5 NSAIDs may exacerbate preexisting conditions such as psoriasis, and may rarely cause serious adverse skin events such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug rash with eosinophilia and systemic symptoms (DRESS).6,7 Topical NSAIDs have been associated with allergic contact dermatitis and with phototoxic and photoallergic contact dermatitis, although the incidence of serious photoallergic reaction while using these agents is extremely rare.8 Of the NSAIDs, those of the propionic acid derivative group, such as naproxen, are the most recognized to cause pseudoporphyria, and the reaction appears unrelated to dose.3 The newer cyclo-oxygenase (COX) 2 inhibitors are not without risk, as celecoxib has now been associated with pseudoporphyria as well.9 Diclofenac is an acetic acid derivative, and had been suggested as a safe alternative NSAID in patients with NSAID-related pseudoporphyria for whom ongoing treatment is required. However, in 2001, diclofenac was reported to have caused pseudoporphyria in a 57-year-old Spanish woman with seronegative rheumatoid arthritis;10 she had been taking diclofenac for 3 months before onset of the pseudoporphyria, and the condition ceased after this medication was stopped. To our knowledge, our patient is only the second reported case of diclofenac-associated pseudoporphyria. Pseudoporphyria induced by diclofenac is vanishingly rare; however, awareness of this scarce association is important for patients requiring ongoing management with NSAIDs.
Clinical and Experimental Dermatology (2014) 39, pp348–350
349
Diclofenac induced pseudoporphyria: an under-recognized condition? N. Turnbull et al.
Learning points ● Pseudoporphyria is a photodistributed bullous
disorder, which is clinically and histologically similar to PCT, but without abnormal porphyrin biochemistry testing. ● Renal failure, dialysis, excessive UVA and medications (particularly the NSAIDs) have been associated with pseudoporphyria. ● To our knowledge, this is only the second reported case in the literature of pseudoporphyria associated with diclofenac, which is considered by many dermatologists as a safe alternative agent in NSAID-induced pseudoporphyria.
References 1 Green JJ, Manders SM. Pseudoporphyria. J Am Acad Dermatol 2001; 44: 100–8. 2 Lang BA, Finlayson LA. Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis. J Pediatr 1994; 124: 639–42.
350
Clinical and Experimental Dermatology (2014) 39, pp348–350
3 O’Donoghue NB, Higgins EM. Case 1: Naproxen-induced pseudoporphyria. Clin Exp Dermatol 2002; 27: 339–40. 4 Kaiser U, Sollberger J, Hoigne R et al. Skin side effects of nonsteroidal anti-inflammatory analgesics and so called minor analgesics. Wochenschr 1987; 117: 1966–70. 5 Sanchez-Borges M, Capriles-Hullett A, Caballero-Fonseca F. Risk of skin reactions when using ibuprofen-based medicines. Expert Opin Drug Saf 2005; 4: 837–48. 6 Ungprasert P, Kittanamongkolchai W, Price C et al. What is the ‘safest” non-steroidal anti-inflammatory drugs? Am Med J 2012; 3: 115–23. 7 Lee JH, Park HK, Heo J et al. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome induced by celecoxib and antituberculosis drugs. J Korean Med Sci 2008; 23: 521–5. 8 Jenerowicz D, Jakubowicz O, Polanska A et al. Photosensitivity to selected topical nonsteroidal anti-inflammatory drugs preparations – a review of literature data and author’s own experience. Cent Eur J Immunol 2011; 36: 197–203. 9 Cummins R, Wagner-Weiner L, Paller A. Pseudoporphyria induced by celecoxib in a patient with juvenile rheumatoid arthritis. J Rheumatol 2000; 27: 2938–40. 10 Zaballos P, Ara M, Echevarra V et al. Pseudoporphyria induced by diclofenac. Atcas Dermosifiliogr 2001; 92: 578–81.
ª 2014 British Association of Dermatologists
