Hydroxychloroquine-induced Hyperpigmentation

 Presented by DJ Elpern

 

This 23-year-old woman presents for evaluation of patchy hyperpigmentation of her face, arms, and abdomen that has been progressing for the past two years.  She has had systemic lupus erythematosus with renal involvement for a decade.  Her current medications include prednisone 15 mg a day, mycophenolic acid, 2 tablets twice a day, hydroxychloroquine (HQ) 400 mg a day, torsemide, Zoloft, olanzapine, losartan, and recently voclosporin.  She has been on 400 mg of HQ since the early days of her Lupus diagnosis.

 

OE:  The examination shows large hyperpigmented patches on the face, ears, arms and in the abdominal striae.  There is no scarring.  She has Cushingoid facies.
 

 

IMPRESSION: Hydroxychloroquine-induced Hyperpigmentation

 

 

PLAN:  We will consult some colleagues with experience in this area and see the patient back in a few weeks.  Recent serologies may be helpful. 

 

Discussion:  HQ hyperpigmentation is well-reported; but most of the articles are small case reports.  It seems to be related to duration of treatment.  This young woman has been on 400 mg of HQ for at least eight years.  Other than stopping HQ, it’s unclear what may help.  The drug may have been of value for her renal disease; but the downside – the hyperpigmentation – is a significant problem for this young person.  So, too is the Cushingoid effects of her prednisone.  A review of the literature was not helpful for therapeutic guidelines regarding the hyperpigmentation other than discontinuing the HQ.

 

 

References:

1. Daniel Kwak, Pearl E Grimes. A case of hyperpigmentation induced by hydroxychloroquine and quinacrine in a patient with systemic lupus erythematosus and review of the literature. Int J Womens Dermatol. 2020 Jun 30;6(4):268-271. Free PMC

 

2. Moez Jallouli. Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case-control study. JAMA Dermatol. 2013 Aug;149(8):935-40.

 

3. Michela Gasparotto et. al. Lupus nephritis: clinical presentations and outcomes in the 21st century. Rheumatology (Oxford). 2020 Dec 5;59(Suppl5):v39-v51.  Free PMC.

 

4. Sendhil Kumaran Muthu. Low-dose oral isotretinoin therapy in lichen planus pigmentosus: an open-label non-randomized prospective pilot study. Int J Dermatol. 2016 Sep;55(9):1048-54. PMID 27062273

 

 

Facial Eruption in a 2 year-old

Presented by Dr. Hamish Thain,  Dundee, Scotland
22 September, 2018

The patient is a 2 yr and 10 month old girl with a few month history of a facial eruption. It began as hive-like plaques but has evolved over the past few weeks.  Her paternal grandmother has Alpha-1 Antitrypsin disease and the child is a carrier.  No family history of collagen vascular disease.  She takes no medications save vitamins.

EXAMINATION:  The examination shows an erythematous papular and nodular eruption on both malar eminences and the left lower lid.   The remainder of the cutaneous exam is unremarkable.

Clinical Photos:

Lab:
CBC, BUN, ANA: all normal or negative.  ESR 7
Urine analysis normal

Pathology:  The slides were read by Deon Wolpowitz and the photmicrographs were taken by Erin Tabata, both of Boston University Department of Skin Pathology.
Intermittent compact hyperkeratosis with parakeratosis, intermittent basal layer vacuolization with squamatization of the basal cell layer and occasional individually necrotic keratinocytes and mild lymphocytic exocytosis, papillary dermal edema that is focally prominent in a few papillae, ectatic blood vessels, and a moderate superficial and deep perivascular and interstitial, and focally periappendageal, lymphohistiocytic infiltrate with few extravasated erythrocytes. 

Diagnosis:  Polymorphous Light variant.  This is not the common papulovesicular variant of PMLE.

Plan:  Initially, she will use broad-spectrum sun-blocks containing zinc oxide or titanium dioxide and a large floppy hat whilst outdoors.  As the season changes, and the light wanes, she should improve.  Topical corticosteroids, calcineurin inhibitors, and hydroxychloroquine will be considered if her parents want further therapy.  Phototesting at a centre is disruptive for this child, at this time.

What are your thoughts.

References
1.Alexis L. Dougherty, Cloyce L. Stetson, MD, Dr. Khachemoune. What are These Facial Plaques in a 4 year-old Child.  The Dermatologist. 8.20.2013  Link

Drug-Induced Lupus?

There are more things in heaven and earth then I dreamt of in our philosophy; and more things that we encounter in our offices than we can find in PubMed’s> 20,000.000 citations.

 A 35-year-old woman was started on a second course of isotretinoin for recurrent acne. Her previous treatment was two years earlier and was uneventful.  A few weeks after restarting the medication, at a dose of 0.5 mg per kilogram per day, she experienced some malaise, muscle aches, and mild joint pain. There were no new skin findings. She called me and I allowed that I had not heard of these symptoms with isotretinoin, but ordered a CBC and an ANA.

The CBC was normal, but the ANA was positive at 1:640 with a homogeneous pattern.   A PubMed search retrieved no references to drug-induced lupus and isotretinoin. However, a Google search found some anecdotal reports and a few cases of suspected DIL with isotretinoin (there were 5 alleged cases of DIL out of 27,831 self- reported isotretinoin side-effects) eHealthme.

With regards to our patient, I am going to repeat her ANA and obtain an anti-histone antibody test. If the ANA is still positive I will have her stop the isotretinoin and repeat the lab studies after 2–3 weeks. Should this likely be DIL then I think it is important that there be a report in the medical literature as undoubtedly other patients will experience this.

New Onset Plaques in an Exchange Student in Malaysia

Presented by Henry Foong
Ipoh, Malaysia

Abstract: 26 yo man with 2 month history of plaques face and chest

HPI:  The patient is a 26-yr-old healthy Libyan student who presented with a two month history of erythematous plaques on the face and chest.  He first noticed the reddish plaques on the chest and subsequently spread to the face.  Presently, it also involves the elbows and knees. It is asymptomatic and does not appear to be transient.  It does not seem to be aggravated by sunlight, heat, cold or physical activity.  He is otherwise well and is not on any long term medications/herbs/OTC.

O/E:  Shows few erythematous raised annular plaques 1-2 cm on the anterior chest wall, forehead, cheek, extensor surfaces of the elbows and knees. They do not blanch with pressure.  There are a few patches of alopecia with underlying erythematous skin noted on the occipital scalp. 

Clinical Images:

 

 

 

Lab: Blood counts and biochemistry were normal.  VDRL was negative. Anti-nuclear antibody serology was 1:320 titre.  

Path: Skin biopsy results: Section shows skin composed of epidermis and dermis. Hyperkeratosis and atrophied epidermis are seen. There is basal layer degeneration. Pigment laden macrophages are seen in the upper dermis. Perivascular lymphocytic infiltrates are seen in the upper and mid dermis. No granulomas are seen.

Diagnosis:  Lupus erythematosus

Plan: The immediate plan is to institute oral prednisolone 30mg daily and hydroxychloroquine 400mg daily with advise on sunblocks. However, on examination by ophthalmologist, he found maculopathy in this patient and raised the question of suitability of hydroxychloroquine in this patient.

Questions
Which type of LE would this patent fit into.  Subacute LE?
Which steroid sparing agent would you use? cellcept or imuran?

Comment by Richard Sontheimer, M.D.

The clinical and histopathologic features are highly suggestive of lupus-specific skin disease. From the photographs I cannot tell if this is subacute cutaneous LE or generalized discoid LE (induration of the lesions would be more consistent with discoid LE). Lesions in the scalp would argue more for discoid LE. However, the positive ANA would be more typical of SCLE. If possible I would check this patient's Ro/SS-A and La/SS-B autoantibody status. It is possible at times to see overlapping features of subacute SCLE and discoid LE concurrently. I would also establish a baseline for possible development of clinically significant systemic LE in the future with the following laboratory screening: Complete blood count with differential, serum chemistry screen, erythrocyte sedimentation rate and urinalysis.

Maculopathy in such a young male is quite unusual. Were there any associated visual field deficits with this maculopathy? If not, I would not exclude the possibility of an ongoing trial of oral hydroxychloroquine or chloroquine with careful ophthalmology followup. In addition, antimalarial therapy with oral quinacrine could be considered as this antimalarial drug does not add risk for retinal toxicity. Thalidomide at could also be considered in such case presuming it was available to the patient and appropriate followup for neurologic toxicity could be assured.

With respect to immunosuppressive steroid-sparing effect I would first consider methotrexate. After that I would consider CellCept as Imuran is relatively more toxic. In addition aggressive topical corticosteroid therapy would also be advised.

Facial flush in a pregnant woman

Presented by Henry Foong

Ipoh, Malaysia

A 37 year old restaurant waitress had these rashes on the face for several years, but worse recently since her pregnancy. She is G2P1 at the end of her first trimester. The rash was described as itching, burning. She had seen a dermatologist in Japan and was diagnosed as rosacea. There was no fever or polyarthralgia. Family history was insignificant. Drug history nil.

She feels very uncomfortable. Examination was unremarkable except facial flushing with for bilateral and symmetrical erythematous papules on both cheeks with a mild involvement of the bridge of nose. There was no comedones. Her scalp was normal.
What do you think of the diagnosis? Do you think this is rosacea? What other differentials would you consider - lupus erythematosus, seborrheic dermatitis? How would you manage her remembering that she 3 months pregnant? Would you use topical metrondazole?

Lupus Erythematosus?

presented by Henry Foong:

A case in progress... 14 year-old Malaysian boy with photosensitive eruption


HPI:The patient is a 14 year old student with one year history of erythematous patches on the face, made worse with sun exposure. He is otherwise healthy with no systemic complaints. He has been on no medications byh mouth.

Examination showed few discrete 2-4 cm erythematous plaques on the cheeks, nose, upper and lower eyelids. No alopecia. No scarring.

I Suspect this is lupus erythematous. Acute LE or Subacute LE ? ANA serology and biopsy done. Results pending. Differentials - Jessner's lymphocytic infiltrates

Questions: What are your thoughts pending the biopsy findings? Would you do anything different from what I have done so far?